Displaying publications 21 - 40 of 52 in total

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  1. Underlying mechanism of vasorelaxant effect exerted by 3,5,7,2',4'-pentahydroxyflavone in rats aortic ring
    Tew WY, Tan CS, Asmawi MZ, Yam MF
    Eur J Pharmacol, 2020 Aug 05;880:173123.
    PMID: 32335091 DOI: 10.1016/j.ejphar.2020.173123
    Morin (3,5,7,2',4'-pentahydroxyflavone) is a yellow coloured natural flavonoid found in plants of the Moraceae family. This favonoid is easily sources from readily available fruits, vegetables and eve certain beverages. Among the sources that was identified, it is clear that morin is most abundantly found in almond, old fustic, Indian guava, and Osage orange. Multiple studies have suggested that morin has multiple therapeutic actions and possess potential to be a functional potent drug. Previous studies demonstrated that morin is capable of resolving deoxycorticosterone acetate-salt-induced hypertension and possess strong vasorelaxant properties. However, the exact mechanisms remains unknown. Therefore, this study is designed to investigate the in vitro mechanism of morin-induced vasorelaxant effects. The underlying mechanisms of morin's vasorelaxant activities were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats. Results from the study demonstrated morin causing vasodilatory reaction in phenylephrine and potassium chloride pre-contracted endothelium-intact aortic rings with the effect being significantly affected in endothelium-denuded aortic rings. Pre-incubation of the aortic rings with ODQ (selective cGMP-independent sGC inhibitor), indomethacin (nonselective COX inhibitor), L-NAME (endothelial nitric oxide inhibitor), propranolol (β2-adrenegic receptors blocker), and atropine (muscarinic receptors blocker) significantly reduced the vasorelaxant effect of morin. It was also found to be able to reduce the intracellular calcium level by blocking VOCC and calcium intake from the extracellular environment and the intracellular release of calcium from the sarcoplasmic reticulum. The present study showed that the vasorelaxant effect of morin potentially involves the NO/sGC, muscarinic receptors, β2-adrenegic receptors, and calcium channels.
    Matched MeSH terms: Phenylephrine/pharmacology
  2. Mechanisms underlining gender differences in Phenylephrine contraction of normoglycaemic and short-term Streptozotocin-induced diabetic WKY rat aorta
    Aloysius UI, Achike FI, Mustafa MR
    Vascul Pharmacol, 2012 Sep-Oct;57(2-4):81-90.
    PMID: 22172524 DOI: 10.1016/j.vph.2011.11.009
    The female gender reduces the risk, but succumbs more to cardiovascular disease. The hypothesis that short-term (8weeks) Streptozotocin-induced diabetes could produce greater female than male vascular tissue reactivity and the mechanistic basis were explored. Aortic ring responses to Phenylephrine were examined in age- and sex-matched normoglycaemic/diabetic rats. The normoglycaemic male tissue contracted significantly more than the normoglycaemic female and the male/female diabetic tissues. Endothelial-denudation, l-NAME or MB reversed these differences suggesting an EDNO-cGMP dependence. 17β-oestradiol exerted relaxant effect on all endothelium-denuded (and normoglycaemic endothelium-intact male) tissues, but not endothelium-intact normoglycaemic female. The greater male tissue contraction is attributable to absent 17β-oestradiol-modulated relaxation. Indomethacin blockade of COX attenuated male normoglycaemic and female diabetic tissue contraction (both reversed by l-NAME), but augmented diabetic male tissue contraction. These data are consistent with the raised contractile TXA(2) and PGE(2) in normoglycaemic male and diabetic female tissues, and the relaxant PGI(2) in diabetic male (and female). The higher levels of PGI(2) in the normoglycaemic and diabetic female perhaps explain their greater relaxant response to Acetylcholine compared to the respective male. In conclusion, there is an endothelium-dependent gender difference in the effect of short term diabetes on vascular tissue reactivity which is COX mediated.
    Matched MeSH terms: Phenylephrine/pharmacology*
  3. Clonidine and a novel clonidine analog AL-12 cause sympathoinhibition in spontaneously hypertensive and diabetic spontaneously hypertensive rats
    Lazahari MI, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Methods Find Exp Clin Pharmacol, 2008 Apr;30(3):193-9.
    PMID: 18597003 DOI: 10.1358/mf.2008.30.3.1166221
    This study examined the sympathoinhibitory effects of clonidine and a novel clonidine analog, AL-12, in rat models of genetic hypertension and a combined state of genetic hypertension and diabetes. Rats in the treatment groups were given either clonidine or AL-12 while the respective control groups received either saline or Tween 80 for 6 days. Physiological data were collected during this period, which was followed by acute studies on day 7 when bolus administrations (i.v.) of graded doses of noradrenaline, phenylephrine and methoxamine were carried out. It was observed that in AL-12-treated nondiabetic spontaneously hypertensive rats (SHR), the pressure responses to all adrenergic agonists were greater (p < 0.05) in the treated group, while in the diabetic SHR rats a larger pressure response was observed only to noradrenaline (p < 0.05). In nondiabetic SHR rats treated with clonidine, a greater (p < 0.05) pressure response was observed only in the case of phenylephrine. In the diabetic SHR rats treated with clonidine, the pressure responses to the adrenergic agonists were similar (p > 0.05) in the treated and its control animals except that methoxamine caused a greater (p < 0.05) pressure response in the control group. The data obtained suggest that clonidine and AL-12 act possibly via vascular alpha1 and alpha2 adrenoceptors present at both pre- and postsynaptic locations.
    Matched MeSH terms: Phenylephrine/pharmacology
  4. Intake of repeatedly heated palm oil causes elevation in blood pressure with impaired vasorelaxation in rats
    Leong XF, Najib MN, Das S, Mustafa MR, Jaarin K
    Tohoku J Exp Med, 2009 Sep;219(1):71-8.
    PMID: 19713687
    Oxidization of dietary cooking oil increases the risk of cardiovascular diseases such as hypertension by increasing the formation oxidative oxygen radicals. The aim of study was to investigate the effects of repeatedly heated palm oil on blood pressure, plasma nitrites, and vascular reactivity. Nitrites were measured, as an indirect marker for nitric oxide production. Male Sprague-Dawley rats were divided into four groups: control group fed with basal diet and other three groups fortified with 15% weight/weight fresh palm oil (FPO), palm oil heated five times (5HPO) or palm oil heated ten times (10HPO) for 24 weeks. The oil was heated to 180 degrees C for 10 min. Blood pressure was measured at baseline and at intervals of four weeks for 24 weeks using non-invasive tail-cuff method. Following 24 weeks, the rats were sacrificed and thoracic aortas were dissected for measurement of vascular reactivity. Blood pressure was elevated significantly (p < 0.05) in 5HPO and 10HPO groups, with the 10HPO group showing higher values. Aortic rings from animals fed with heated oil showed diminished relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Acetylcholine and sodium nitroprusside cause endothelium-dependent and endothelium-independent relaxation, respectively. Relaxation responses remained unaltered in the FPO group, with the attenuated contractile response to phenylephrine, compared to control group. FPO increased plasma nitrites by 28%, whereas 5HPO and 10HPO reduced them by 25% and 33%, respectively. Intake of repeatedly heated palm oil causes an increase in blood pressure, which may be accounted for by the attenuated endothelium-dependent vasorelaxant response.
    Matched MeSH terms: Phenylephrine/pharmacology
  5. Comparison of mydriatic regimens used in screening for retinopathy of prematurity in preterm infants with dark irides
    Chew C, Rahman RA, Shafie SM, Mohamad Z
    J Pediatr Ophthalmol Strabismus, 2005 6 28;42(3):166-73.
    PMID: 15977870
    PURPOSE: To determine the mydriatic regimen that provides optimal dilation of the pupil with minimal systemic side effects for screening of retinopathy of prematurity.

    METHODS: This cross-sectional, randomized, double-masked clinical trial compared cyclopentolate 1% + phenylephrine 2.5%, tropicamide 1% + phenylephrine 2.5%, and a prepared combination of cyclopentolate 0.2% with phenylephrine 1% for pupillary dilation in preterm infants with dark irides. Thirteen infants were randomized to each regimen. Outcomes measured were pupillary dilation, heart rate, blood pressure, abdominal girth, and intolerance to feeds.

    RESULTS: All three mydriatic regimens provided adequate pupillary dilation at 45 minutes, with dilation sustained at 60 minutes. There was a significant increase in mean blood pressure in the cyclopentolate 1% + phenylephrine 2.5% and the tropicamide 1% + phenylephrine 2.5% groups. Although there was no significant change of abdominal girth in any of the three groups, a total of eight patients developed intolerance to feeds; four (50%) of these infants were from the cyclopentolate 1% + phenylephrine 2.5% group.

    CONCLUSION: The prepared combination of cyclopentolate 0.2% + phenylephrine 1% appears to be the mydriatic of choice for preterm infants with dark irides as it provided adequate pupillary dilation with the least systemic side effects.

    Matched MeSH terms: Phenylephrine/administration & dosage
  6. Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta
    Machha A, Mustafa MR
    J Cardiovasc Pharmacol, 2005 Jul;46(1):36-40.
    PMID: 15965352
    Flavonoids are known to possess cardioprotective properties. Vascular endothelial function is a surrogate marker for cardiovascular diseases, including hypertension. We have studied the effects of chronic flavonoid treatment on vascular endothelial functions in spontaneously hypertensive rats (SHR). Starting from 6-7 weeks old, SHR were given flavonoids (baicalein, flavone, or quercetin) orally (10 mg/kg, once daily) to the SHRs for 4 weeks. Aortas from all the flavonoid-treated animals showed remarkably higher endothelium-dependent relaxations to acetylcholine, to a similar extent as those pretreated with the angiotensin-converting enzyme inhibitor, captopril. However, in contrast to other experimental groups, flavone pretreatment also enhanced the endothelium-independent relaxations to sodium nitroprusside. In addition, treatment with either flavone or quercetin induced a significant attenuation in systolic blood pressure of the hypertensive animals. The present results suggest that chronic treatment with the flavonoids (baicalein, flavone, and quercetin) preserves vascular endothelial functions in hypertensive animals through several possible actions, including increasing endothelial nitric oxide production and bioavailability and reduction in blood pressure.
    Matched MeSH terms: Phenylephrine/pharmacology
  7. In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats
    Lim YL, Mok SL
    Med Princ Pract, 2010;19(4):260-8.
    PMID: 20516701 DOI: 10.1159/000312711
    To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro.
    Matched MeSH terms: Phenylephrine/pharmacology
  8. Contractile function of smooth muscle retained after overnight storage
    Loong BJ, Tan JH, Lim KH, Mbaki Y, Ting KN
    Naunyn Schmiedebergs Arch Pharmacol, 2015 Oct;388(10):1061-7.
    PMID: 26051407 DOI: 10.1007/s00210-015-1140-3
    The functional responses of different overnight-stored in vitro tissues are not clearly described in any animal model. The influence of overnight storage in an animal model may vary between tissue types. We employed Sprague-Dawley rat as our animal model and investigated the functional changes of rat aorta, trachea, bronchus and bladder that were used (i) immediately after surgical removal (denoted as fresh) and (ii) after storage in aerated (95% O2, 5% CO2) Krebs-Ringer bicarbonate solution at 4 °C for 24 h (denoted as stored). The aorta ring was pre-contracted with phenylephrine, and the functional response of the tissue was investigated using isoprenaline, forskolin and carbachol. Carbachol was also used to increase the tone in trachea, bronchus rings and bladder strips. A clear reduced function of endothelium, with a minor if any effect in the smooth muscle function in rat aorta was observed after overnight storage. The contractile response of overnight-stored rat airway (trachea and bronchus) and bladder smooth muscles remained unchanged. Among all tested tissues, only bronchus showed a reduced response rate (only 40% responded) after storage. In vitro rat tissues that are stored in Krebs solution at 4 °C for 24 h can still be used to investigate smooth muscle responses, however, not endothelium-mediated responses for aorta. The influence of overnight storage on different tissues from an animal model (Sprague-Dawley rat in our study) also provides an insight in maximising the use of sacrificed animals.
    Matched MeSH terms: Phenylephrine/pharmacology
  9. Fulltext Renoprotective and haemodynamic effects of adiponectin and peroxisome proliferator-activated receptor agonist, pioglitazone, in renal vasculature of diabetic Spontaneously hypertensive rats
    Afzal S, Abdul Sattar M, Johns EJ, Eseyin OA
    PLoS One, 2020;15(11):e0229803.
    PMID: 33170841 DOI: 10.1371/journal.pone.0229803
    Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5μg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P<0.05] which were normalized by the individual drug treatments and to greater degree following combined treatment. Responses to intra-renal administration of NA, PE, ME and ANGII were larger in diabetic SHR than WKY and SHRs [P<0.05]. Adiponectin significantly blunted responses to NA, PE, ME and ANG II in diabetic treated SHRs by 40%, whereas the pioglitazone combined therapy with adiponectin further attenuated the responses to adrenergic agonists by 65%. [all P <0.05]. These findings suggest that adiponectin possesses renoprotective effects and improves renal haemodynamics through adiponectin receptors and PPAR-γ in diabetic SHRs, suggesting that synergism exists between adiponectin and pioglitazone. A cross-talk relationship also supposed to exists between adiponectin receptors, PPAR-γ and alpha adrenoceptors in renal vasculature of diabetic SHRs.
    Matched MeSH terms: Phenylephrine
  10. Fulltext Intracellular stored calcium plays a minor role in Gq-coupled receptor-mediated contraction in rat airway smooth muscle
    Govindaraju, Kayatri, Lee, Mei Kee, Mbaki, Yvonne, Ting, Kang Nee
    Life Sciences, Medicine and Biomedicine, 2018;2(2):1-6.
    MyJurnal
    The general notion of activation of Gq-protein coupled receptors (GPCR) involves the mobilisation of stored and extracellular calcium and leads to smooth muscle tissue contraction. The aim of this study was to investigate the involvement of calcium mediated contractions in vascular and airway smooth muscles. Using standard organ bath procedures, aortic and tracheal rings were obtained from 6 to 8 week-old male Sprague Dawley rats. To activate the Gq protein receptors, phenylephrine (PE), an α1-adrenoceptor agonist, and carbachol, a M3 cholinoceptor agonist was added to baths containing the aortic and tracheal rings, respectively. The maximum response (Emax) to PE was reduced from 158.8 ± 11.8% (n=6) to 62.5 ± 12.4 % (n=8) upon removal of extracellular calcium in Krebs-Ringer solution. Maximal response to PE was also suppressed in the presence of nifedipine, a L-type Ca2+ channel inhibitor, (70.3 ± 11 %, n=8) and SKF96365, a canonical transient receptor potential cation channel inhibitor, (26.7 ± 13.2 %, n=5) when the influx of extracellular calcium was blocked. Removal of stored calcium also attenuated the PE contraction (p0.05). From these observations, we conclude that the role of stored and extracellular calcium in Gq protein activation is not the same across different types of smooth muscle tissues.
    Matched MeSH terms: Phenylephrine
  11. The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats
    Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ
    Br J Pharmacol, 2004 Jun;142(4):719-26.
    PMID: 15172958
    1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
    Matched MeSH terms: Phenylephrine/administration & dosage; Phenylephrine/antagonists & inhibitors; Phenylephrine/pharmacokinetics
  12. Characterization of a novel tetrandrine-induced contraction in rat tail artery
    Achike FI, Kwan CY
    Acta Pharmacol Sin, 2002 Aug;23(8):698-704.
    PMID: 12147191
    In an attempt to pharmacologically characterize the Chinese antihypertensive drug, tetrandrine, we observed in rat-tail arteries, an unusual contraction in tissues that were stimulated with high [KCl] and not those stimulated with phenylephrine. The characteristics of this contraction were studied.
    Matched MeSH terms: Phenylephrine
  13. Fulltext Erectogenic Effects of Clerodendron capitatum: Involvement of Phosphodiesterase Type-5 Inhibition
    Abdelwahab SI, Mohamed AH, Mohamed OY, Oall M, Taha MM, Mohan S, et al.
    Evid Based Complement Alternat Med, 2012;2012:137386.
    PMID: 21747892 DOI: 10.1155/2012/137386
    Clerodendron capitatum (Willd) (family: verbenaceae) is locally named as Gung and used traditionally to treat erectile dysfunction. Therefore, the current study was designed to investigate the erectogenic properties of C. capitatum. The relaxation effect of this plant was tested on phenylephrine precontracted rabbit corpus cavernosum smooth muscle (CCSM). The effects of C. capitatum were also examined on isolated Guinea pig atria alone, in the presence of calcium chloride (Ca(2+) channel blocker), atropine (cholinergic blocker), and glibenclamide (ATP-sensitive K(+) channel blocker). These effects were confirmed on isolated rabbit aortic strips. The extract, when tested colorimetrically for its inhibitory activities on phosphordiesterase-5 (PDE-5) in vitro towards p-nitrophenyl phenyl phosphate (PNPPP), was observed to induce significant dose-dependent inhibition of PDE-5, with an ID(50) of 0.161 mg/ml (P < .05). In conclusion, our results suggest that C. capitatum possesses a relaxant effect on CCSM, which is attributable to the inhibition of PDE-5, but not mediated by the release calcium, activation of adrenergic or cholinergic receptors, or the activation of potassium channels.
    Matched MeSH terms: Phenylephrine
  14. Effects of citrus leaf extract on aortic vascular reactivity in hypertensive rats fed repeatedly heated vegetable oil
    Siti HN, Kamisah Y, Mohamed S, Jaarin K
    Appl Physiol Nutr Metab, 2019 04;44(4):373-380.
    PMID: 30216735 DOI: 10.1139/apnm-2018-0175
    The prolonged intake of diet containing repeatedly heated vegetable oil can cause hypertension in the long run.
    In this study, the effects of citrus leaf extract (CLE) supplementation on vascular reactivity, plasma nitrite, and aortic structure in hypertensive rats were investigated by the consumption of repeatedly heated vegetable oil [corrected]. Male Sprague Dawley rats (n = 56) were divided into 7 groups corresponding to the respective diets. For 16 weeks, 1 group was given standard rat chow (control) while other groups were given diets containing 15% w/w of palm oil, fresh palm oil (FPO), palm oil heated 5 times (5HPO), and palm oil heated 10 times (10HPO), with or without the incorporation of 0.15% w/w CLE (FPO+CLE, 5HPO+CLE, or 10HPO+CLE). Plasma nitrite levels were measured before and at 16 weeks of treatment. After 16 weeks, the rats were sacrificed and aortae were harvested for measuring vascular reactivity and for microscopic study. CLE supplementation had significantly reduced the loss of plasma nitrite and attenuated the vasoconstriction response to phenylephrine in the 5HPO group but not in the 10HPO group. However, CLE had no significant effect on the vasorelaxation response to acetylcholine and sodium nitroprusside. The elastic lamellae of tunica media in 5HPO, 10HPO, and 10HPO+CLE groups appeared disorganised and disrupted. Obtained findings suggested that CLE was able to enhance nitric oxide bioavailability that might dampen the vasoconstriction effect of phenylephrine.
    Matched MeSH terms: Phenylephrine/pharmacology
  15. Fulltext Clinacanthus nutans Leaves Extract Reverts Endothelial Dysfunction in Type 2 Diabetes Rats by Improving Protein Expression of eNOS
    Azemi AK, Mokhtar SS, Rasool AHG
    Oxid Med Cell Longev, 2020;2020:7572892.
    PMID: 32879653 DOI: 10.1155/2020/7572892
    Diabetes mellitus is associated with endothelial dysfunction; it causes progressive vascular damage resulting from an impaired endothelium-dependent vasorelaxation. In the diabetes state, presence of hyperglycemia and insulin resistance predisposes to endothelial dysfunction. Clinacanthus nutans, widely used as a traditional medicine for diabetes is reported to have hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory properties. However, the possibility of C. nutans affecting the vascular endothelial function in diabetes remains unclear. This study was aimed at evaluating the effects of C. nutans methanolic leaves extract (CNME) on endothelial function in a type 2 diabetes (T2DM) rat model. Sixty male Sprague-Dawley rats were divided into five groups (n = 12 per group): nondiabetic control, nondiabetic treated with four weeks of CNME (500 mg/kg/daily), untreated diabetic rats, diabetic treated with metformin (300 mg/kg/daily), and diabetic treated with CNME (500 mg/kg/daily). T2DM was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) to rats fed with high-fat diet (HFD). Endothelial-dependent and endothelial-independent relaxations and contractions of the thoracic aorta were determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS) expression was determined using Western blotting. Endothelial-dependent relaxation was reduced in diabetic rats. Both diabetic groups treated with CNME or metformin significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of aortic eNOS protein. CNME- and metformin-treated groups also reduced aortic endothelium-dependent and aortic endothelium-independent contractions in diabetics. Both of these diabetic-treated groups also reduced blood glucose levels and increased body weight compared to the untreated diabetic group. In conclusion, C. nutans improves endothelial-dependent vasodilatation and reduces endothelial-dependent contraction, thus ameliorating endothelial dysfunction in diabetic rats. This may occur due to its effect on increasing eNOS protein expression.
    Matched MeSH terms: Phenylephrine/pharmacology
  16. Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR-γ), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats
    Afzal S, Sattar MA, Johns EJ, Abdulla MH, Akhtar S, Hashmi F, et al.
    J Physiol Biochem, 2016 Dec;72(4):593-604.
    PMID: 27405250
    Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2.5 μg/kg/day) for last 7 days. Groups of SHR received either irbesartan or adiponectin or in combination. A group of Wistar Kyoto rats (WKY) served as controls. Metabolic data and plasma samples were taken on days 0, 21, and 28. In acute studies, the renal vasoconstrictor actions of angiotensin II (ANGII), noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) were determined. SHR control rats had a higher mean blood pressure than the WKY (132 ± 7 vs. 98 ± 2 mmHg), lower plasma and urinary adiponectin, creatinine clearance, urine flow rate and sodium excretion, and oxidative stress markers compared to WKY (all P 
    Matched MeSH terms: Phenylephrine/pharmacology
  17. Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats
    Si LY, Kamisah Y, Ramalingam A, Lim YC, Budin SB, Zainalabidin S
    Appl Physiol Nutr Metab, 2017 Jul;42(7):765-772.
    PMID: 28249121 DOI: 10.1139/apnm-2016-0506
    Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) Cmax = 234.5 ± 3.9%, Endo-(-) Cmax = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) Cmax = 264.5 ± 6.9%, Endo-(-) Cmax = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) Rmax = 73.2 ± 2.1%, Endo-(-) Rmax = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) Rmax = 57.8 ± 1.7%, Endo-(-) Rmax = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.
    Matched MeSH terms: Phenylephrine/pharmacology
  18. Fulltext Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D-Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress
    Wee CL, Mokhtar SS, Singh KKB, Yahaya S, Leung SWS, Rasool AHG
    Oxid Med Cell Longev, 2021;2021:3109294.
    PMID: 33623633 DOI: 10.1155/2021/3109294
    Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.
    Matched MeSH terms: Phenylephrine/pharmacology
  19. Effect of acute unilateral renal denervation on renal hemodynamics in spontaneously hypertensive rats
    Abdulla MH, Sattar MA, Salman IM, Abdullah NA, Ameer OZ, Khan MA, et al.
    Auton Autacoid Pharmacol, 2008 Apr-Jul;28(2-3):87-94.
    PMID: 18598290 DOI: 10.1111/j.1474-8673.2008.00421.x
    1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation. 2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg(-1) i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II. 3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats. 4 The data obtained in denervated rats suggested an enhanced sensitivity of the alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT(1) and alpha(1)-adrenoceptor subtypes.
    Matched MeSH terms: Phenylephrine/pharmacology
  20. Effect of acidosis on the mechanism(s) of insulin-induced vasorelaxation in normal Wistar-Kyoto (WKY) rat aorta
    Subramaniam G, Achike FI, Mustafa MR
    Regul. Pept., 2009 Jun 5;155(1-3):70-5.
    PMID: 19362578 DOI: 10.1016/j.regpep.2009.04.008
    The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar-Kyoto (WKY) rats) with (+ED) or without (-ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic (pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 microM)-contracted tissues were exposed to insulin in the presence or absence of various inhibitors. Insulin exerted similar concentration-dependent relaxation of +ED tissues in normal and acidotic pH. Endothelium denudation, significantly (p<0.05) reduced insulin effect in normal, but not acidotic pH. Under normal pH, treatment with L-NAME or methylene blue significantly (p<0.05) reduced insulin responses in the +ED (but not the -ED) tissues. The insulin effect was also significantly (p<0.05) inhibited by tetraethylammonium (TEA; BK(Ca) blocker), 4-Aminopyridine (4-AP; K(V) channel blocker), combined treatments (L-NAME+4-AP+TEA, in +ED tissues) or (4-AP+TEA, in -ED tissues). In either +ED or -ED tissues, indomethacin (cyclo-oxygenase inhibitor), glibenclamide (K(ATP) channel blocker), barium chloride (K(ir) channel blocker) or Ouabain (a Na(+)/K(+)-ATPase inhibitor) had no effect. Except for methylene blue (effect on +ED tissues), none of the drug treatments inhibited insulin vasodilator effect in acidosis (+ED or -ED tissues). These data indicate that insulin exerts an endothelium-dependent and -independent vasodilatation in rat aorta which in normal pH is mediated via BK(Ca) and K(v) channels, including the EDNO-cGMP cascade. Acidosis abolishes the endothelium-dependent relaxation mechanism unraveling a novel mechanism that is as efficacious and is cGMP-, but not EDNO-, BK(Ca)- or K(v)-mediated.
    Matched MeSH terms: Phenylephrine/pharmacology
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