MyMedR

Displaying publications 21 - 39 of 39 in total

Abstract:

Sort:

Fulltext Effect of the antihypertensive drug enalapril on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat

Chandran G, Sirajudeen KN, Yusoff NS, Swamy M, Samarendra MS

Oxid Med Cell Longev, 2014;2014:608512.
PMID: 25254079 DOI: 10.1155/2014/608512

Oxidative stress has been suggested to play a role in hypertension and hypertension induced organ damage. This study examined the effect of enalapril, an antihypertensive drug, on oxidative stress markers and antioxidant enzymes in kidney of spontaneously hypertensive rat (SHR) and Nω -nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups (SHR, SHR+enalapril, SHR+L-NAME, and SHR+enalapril+L-NAME). Enalapril (30 mg kg(-1) day(-1)) was administered from week 4 to week 28 and L-NAME (25 mg kg(-1) day(-1)) was administered from week 16 to week 28 in drinking water. Systolic blood pressure (SBP) was measured during the experimental period. At the end of experimental periods, rats were sacrificed; urine, blood, and kidneys were collected for the assessment of creatinine clearance, total protein, total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and catalase (CAT), as well as histopathological examination. Enalapril treatment significantly enhanced the renal TAS level (P < 0.001) and SOD activity (P < 0.001), reduced the TBARS levels (P < 0.001), and also prevented the renal dysfunction and histopathological changes. The results indicate that, besides its hypotensive and renoprotective effects, enalapril treatment also diminishes oxidative stress in the kidneys of both the SHR and SHR+L-NAME groups.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Indole alkaloids and anti-nociceptive mechanisms of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract

Ali Khan MS, Misbah, Ahmed N, Arifuddin M, Rehman A, Ling MP

Food Chem Toxicol, 2018 Jun 05.
PMID: 29883785 DOI: 10.1016/j.fct.2018.06.007

Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Vasorelaxant effect of water fraction of Labisia Pumila and its mechanisms in spontaneously hypertensive rats aortic ring preparation

Manshor NM, Razali N, Jusoh RR, Asmawi MZ, Mohamed N, Zainol S, et al.

Int J Cardiol Hypertens, 2020 Mar;4:100024.
PMID: 33447753 DOI: 10.1016/j.ijchy.2020.100024

Introduction: Labisia pumila has been reported to possess activities including antioxidant, anti-aging and anti-cancer but there is no report on its vasorelaxant effects.
Objective: This study aims to fractionate water extract of Labisia pumila, identify the compound(s) involved and elucidate the possible mechanism(s) of its vasorelaxant effects.
Methods: Water extract of Labisia pumila was subjected to liquid-liquid extraction to obtain ethyl acetate, n-butanol and water fractions. In SHR aortic ring preparations, water fraction (WF-LPWE) was established as the most potent fraction for vasorelaxation. The pharmacological mechanisms of the vasorelaxant effect of WF-LPWE were investigated with and without the presence of various inhibitors. The cumulative dose-response curves of potassium chloride (KCl)-induced contractions were conducted to study the possible mechanisms of WF-LPWE in reducing vasoconstriction.
Results: WF-LPWE produced dose-dependent vasorelaxant effect in endothelium-denuded aortic ring and showed non-competitive inhibition of dose-response curves of PE-induced contraction, and at its higher concentrations reduced KCl-induced contraction. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly inhibited vasorelaxant effect of WF-LPWE. WF-LPWE significantly reduced the release of intracellular calcium ion (Ca2+) from the intracellular stores and suppressed the calcium chloride (CaCal2)-induced contraction. Nω-nitro-L-arginine methyl ester (L-NAME), methylene blue, indomethacin and atropine did not influence the vasorelaxant effects of WF-LPWE.
Conclusion: WF-LPWE exerts its vasorelaxant effect independently of endothelium and possibly by inhibiting the release of calcium from intracellular calcium stores, receptor-operated calcium channels and formation of inositol 1,4,5- triphosphate. WF-LPWE vasorelaxant effect may also mediated via nitric oxide-independent direct involvement of soluble guanylate cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathways.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Fulltext Autonomic Nervous System Mediates the Hypotensive Effects of Aqueous and Residual Methanolic Extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum Leaves in Anaesthetized Rats

Ismail A, Mohamed M, Sulaiman SA, Wan Ahmad WA

Evid Based Complement Alternat Med, 2013;2013:716532.
PMID: 24454508 DOI: 10.1155/2013/716532

Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S. polyanthum leaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion and α -adrenergic receptors using hexamethonium and phentolamine (n = 5 for each group) partially attenuated AESP-induced hypotension, suggesting involvement of α -adrenergic receptors. Blockages of autonomic ganglion, β -adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N- ω -nitro-l arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement of β -adrenergic and cholinergic receptors via nitric oxide production.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Fulltext Methanolic Extract of Clinacanthus nutans Exerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways

Abdul Rahim MH, Zakaria ZA, Mohd Sani MH, Omar MH, Yakob Y, Cheema MS, et al.

Evid Based Complement Alternat Med, 2016;2016:1494981.
PMID: 27190528 DOI: 10.1155/2016/1494981

The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract of Clinacanthus nutans (Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p < 0.05) antinociceptive response in all nociceptive models with the recorded ED50 value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed by l-arginine (l-arg; a nitric oxide [NO] precursor), Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract's antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Parkia speciosa empty pod prevents hypertension and cardiac damage in rats given N(G)-nitro-l-arginine methyl ester

Kamisah Y, Zuhair JSF, Juliana AH, Jaarin K

Biomed Pharmacother, 2017 Dec;96:291-298.
PMID: 28992471 DOI: 10.1016/j.biopha.2017.09.095

Parkia speciosa Hassk is a plant found abundantly in Southeast Asia region. Its seeds with or without pods and roots have been used in traditional medicine in this region to treat hypertension. Therefore, we aimed to investigate the potential effect of the plant empty pod extract on hypertension development and changes in heart induced by N(G)-nitro-l-arginine methyl ester (l-NAME) administration in rats. Twenty-four male Sprague Dawley rats were divided into four groups. Groups 1 to 3 were given l-NAME (25mg/kg, intraperitoneally) for 8 weeks. Groups 2 and 3 were also given Parkia speciosa empty pods methanolic extract (800mg/kg, orally) and nicardipine (3mg/kg, orally), concurrently with l-NAME. The last group served as the control. l-NAME reduced plasma nitric oxide level and therefore, increased systolic blood pressure, angiotensin-converting enzyme and NADPH oxidase activities as well as lipid peroxidation in the heart. Parkia speciosa extract and nicardipine treatments had significantly prevented the elevations of blood pressure, angiotensin-converting enzyme, NADPH oxidase activities and lipid peroxidation in the heart induced by the l-NAME. Parkia speciosa extract but not nicardipine prevented the reduction in plasma nitric oxide level caused by l-NAME. In conclusion, Parkia speciosa empty pods methanolic extract has a potential to prevent the development of hypertension possibly by preventing the loss of plasma nitric oxide, as well as has cardioprotective effects by reducing angiotensin-converting enzyme activity and oxidative stress in the heart in rats administered l-NAME.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/toxicity*
Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta

Ajay M, Gilani AU, Mustafa MR

Life Sci, 2003 Dec 19;74(5):603-12.
PMID: 14623031

The potency, structure-activity relationship, and mechanism of vasorelaxation of a series of flavonoids, representing different subclasses (flavonols: fisetin, rutin, quercetin; flavones: chrysin, flavone, baicalein; flavanones: naringenin, naringin; isoflavones: diadzein and flavanes: epigallo catechin gallate), were examined in the isolated rat aorta. Most of the flavonoids tested showed concentration dependent relaxant effects against K+ (80 mM) and phenylephrine (PE, 0.1 microM)-induced contractions with a greater inhibition of the responses to the alpha1-adrenoceptor agonist. The relaxant effects of most of the flavonoids involve in part the release of nitric oxide and prostaglandins from the endothelium as pretreatment with L-NAME and indomethacin attenuated the responses. In addition, the relaxant action of the flavonoids includes inhibition of Ca+2 influx and release of Ca+2 from intracellular stores. A structure-activity relationship amongst the flavonoids was suggested.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Hepatoprotective potential of glyceryl trinitrate against chemically induced oxidative stress and hepatic injury in rats

Rahman A, Vasenwala SM, Iqbal M

Hum Exp Toxicol, 2017 Aug;36(8):785-794.
PMID: 27758841 DOI: 10.1177/0960327116665675

Glyceryl trinitrate (GTN) has been used widely as a potent vasodilator to treat heart conditions, such as angina pectoris and chronic heart failure. This study aims to elucidate the effect of exogenous nitric oxide (NO) administration, using GTN, on carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in rats. The results obtained demonstrated that NO generated by the administration of GTN affords protection against CCl4-induced oxidative stress and liver injury. Administration of CCl4resulted in a significant ( p < 0.001) increase in lipid peroxidation and tissue damage markers (aspartate and alanine transaminase and lactate dehydrogenase) release in serum. Parallel to these changes, CCl4also caused downregulation of antioxidant enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), and several fold induction in γ-glutamyl transpeptidase (GGT) activity. Subsequent administration of GTN resulted in significant ( p < 0.001) recovery of GSH-metabolizing enzymes in a dose-dependent manner. Further, administration of NO inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), exacerbated CCl4-induced oxidative tissue injury. Overall, the study suggests that GTN might suppress oxidant-induced tissue injury and hepatotoxicity in rats.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Gynura procumbens causes vasodilation by inhibiting angiotensin II and enhancing bradykinin actions

Poh TF, Ng HK, Hoe SZ, Lam SK

J Cardiovasc Pharmacol, 2013 May;61(5):378-84.
PMID: 23328388 DOI: 10.1097/FJC.0b013e31828685b3

Previous studies showed that Gynura procumbens reduced blood pressure by blocking calcium channels and inhibiting the angiotensin-converting enzyme activity. The present experiments were to further explore the effects and mechanisms of a purer aqueous fraction (FA-I) of G. procumbens on angiotensin I (Ang I)-induced and angiotensin II (Ang II)-induced contraction of aortic rings and also on the bradykinin (BK) effect on cardiovascular system. Rat aortic rings suspended in organ chambers were used to investigate the vascular reactivity of FA-I. Effect of FA-I on BK was studied by in vitro and in vivo methods. Results show that FA-I significantly (P < 0.05) decreased the contraction evoked by Ang I and Ang II. In the presence of indomethacin (10 µM) or N-nitro-L-arginine methyl ester (0.1 µM), the inhibitory effect of FA-I on Ang II-induced contraction of aortic rings was reduced. Besides, FA-I potentiated the vasorelaxant effect and enhanced the blood pressure-lowering effect of BK. In conclusion, FA-I reduced the contraction evoked by Ang II probably via the endothelium-dependent pathways, which involve activation of the release of nitric oxide and prostaglandins. The inhibition of angiotensin-converting enzyme activity by FA-I may contribute to the potentiation of the effects of BK on cardiovascular system.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
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: NG-Nitroarginine Methyl Ester/pharmacology
The antinociceptive activity of Muntingia calabura aqueous extract and the involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in its observed activity in mice

Zakaria ZA, Sulaiman MR, Jais AM, Somchit MN, Jayaraman KV, Balakhrisnan G, et al.

Fundam Clin Pharmacol, 2006 Aug;20(4):365-72.
PMID: 16867020

The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Direct effects of quercetin on impaired reactivity of spontaneously hypertensive rat aortae: comparative study with ascorbic acid

Ajay M, Achike FI, Mustafa AM, Mustafa MR

Clin Exp Pharmacol Physiol, 2006 Apr;33(4):345-50.
PMID: 16620299

1. There is a growing interest in the anti-oxidant characteristics and use of flavonoids in the management of cardiovascular diseases. The cardiovascular mechanism of action of these plant derivatives remains controversial. This study compared the effects of the flavonoid quercetin with those of the anti-oxidant vitamin ascorbic acid (vitamin C) on the reactivity of aortic rings from spontaneously hypertensive rats (SHR). 2. The phenylephrine (PE)-induced contractile and the endothelium-dependent and independent relaxant responses of aortic rings from 21 to 22 week old SHR and age-matched normotensive Wistar (WKY) rats were observed in the presence of quercetin or ascorbic acid. All the experiments were performed in the presence of the cyclooxygenase inhibitor, indomethacin (10 micromol/L). 3. The endothelium-dependent and independent relaxations to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly lesser in the SHR compared to the WKY tissues whereas the contractile responses to PE were similar in both tissues. Pretreatment of WKY rings with quercetin or ascorbic acid had no effect on the responses to ACh or PE. In the SHR tissues, however, quercetin or ascorbic acid significantly improved the relaxation responses to ACh and reduced the contractions to PE with greater potency for quercetin. Both compounds lacked any effects on the responses to SNP in either aortic ring types. N(omega)-nitro-L-arginine methyl ester (l-NAME, 10 micromol/L) significantly attenuated the vasodepressor effects of quercetin and ascorbic acid, raising the responses to PE to a level similar to that observed in the control SHR tissues. In l-NAME pretreated aortic rings, quercetin and ascorbic acid inhibited the contractile responses to PE with the same magnitude in WKY and SHR tissues. 4. The present results suggest that acute exposure to quercetin improves endothelium-dependent relaxation and reduces the contractile responses of hypertensive aortae with a greater potency than ascorbic acid. This suggests a better vascular protection with this flavonoid than ascorbic acid in the SHR model of hypertension and possibly in human cardiovascular diseases.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Anti-inflammatory activities of cucurbitacin E isolated from Citrullus lanatus var. citroides: role of reactive nitrogen species and cyclooxygenase enzyme inhibition

Abdelwahab SI, Hassan LE, Sirat HM, Yagi SM, Koko WS, Mohan S, et al.

Fitoterapia, 2011 Dec;82(8):1190-7.
PMID: 21871542 DOI: 10.1016/j.fitote.2011.08.002

The in vivo and in vitro mechanistic anti-inflammatory actions of cucurbitacin E (CE) (Citrullus lanatus var. citroides) were examined. The results showed that LPS/INF-γ increased NO production in RAW264.7 macrophages, whereas L-NAME and CE curtailed it. CE did not reveal any cytotoxicity on RAW264.7 and WRL-68 cells. CE inhibited both COX enzymes with more selectivity toward COX-2. Intraperitoneal injection of CE significantly suppressed carrageenan-induced rat's paw edema. ORAC and FRAP assays showed that CE is not a potent ROS scavenger. It could be concluded that CE is potentially useful in treating inflammation through the inhibition of COX and RNS but not ROS.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Fulltext Mesenchymal stem cells exert anti-proliferative effect on lipopolysaccharide-stimulated BV2 microglia by reducing tumour necrosis factor-α levels

Jose S, Tan SW, Ooi YY, Ramasamy R, Vidyadaran S

J Neuroinflammation, 2014;11:149.
PMID: 25182840 DOI: 10.1186/s12974-014-0149-8

Progression of neurodegenerative diseases occurs when microglia, upon persistent activation, perpetuate a cycle of damage in the central nervous system. Use of mesenchymal stem cells (MSC) has been suggested as an approach to manage microglia activation based on their immunomodulatory functions. In the present study, we describe the mechanism through which bone marrow-derived MSC modulate the proliferative responses of lipopolysaccharide-stimulated BV2 microglia.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Fulltext No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats

Hong YH, Betik AC, Premilovac D, Dwyer RM, Keske MA, Rattigan S, et al.

Am J Physiol Regul Integr Comp Physiol, 2015 May 15;308(10):R862-71.
PMID: 25786487 DOI: 10.1152/ajpregu.00412.2014

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Modulation of vascular reactivity in normal, hypertensive and diabetic rat aortae by a non-antioxidant flavonoid

Ajay M, Achike FI, Mustafa MR

Pharmacol Res, 2007 May;55(5):385-91.
PMID: 17317209

In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.

Matched MeSH terms: NG-Nitroarginine Methyl Ester/pharmacology
Hydrogen peroxide modulates angiotensin II-induced contraction of mesenteric arteries from streptozotocin-induced diabetic rats

Chin LC, Achike FI, Mustafa MR

Vascul Pharmacol, 2007 Mar;46(3):223-8.
PMID: 17126611 DOI: 10.1016/j.vph.2006.10.005

Hydrogen peroxide (H(2)O(2)) contributes in the regulation of vascular tone, especially in pathological states. The role of H(2)O(2) and superoxide anion free radicals in angiotensin II (Ang II)-induced contraction of diabetic tissues was examined with the aim of elucidating the underlying mechanisms. Isometric tension in response to various drug treatments was measured in isolated superior mesenteric arteries of streptozotocin (STZ)-induced diabetic WKY rats using the Mulvany wire myograph. Compared to the normal (euglycaemic) arteries, the Ang II-induced contraction was significantly reduced in diabetic arteries. Superoxide dismutase (SOD; converts superoxide to H(2)O(2)) significantly reduced the contraction in both types of arteries -- an effect abolished by catalase (H(2)O(2) scavenger), suggesting that the SOD effect was mediated by H(2)O(2). Treatment with catalase had no effect on the Ang II contraction in euglycaemic arteries, but it raised the contraction in diabetic arteries to euglycaemic levels. This increase was similar to that observed with diabetic arteries incubated with L-NAME. Combined catalase and L-NAME treatment further enhanced the contraction in diabetic arteries, suggesting that the catalase effect was not mediated by nitric oxide (NO). The catalase effect was abolished by indomethacin treatment. These results suggest that attenuation of Ang II-induced contraction in diabetic tissues is modulated by endogenous H(2)O(2), the scavenging of which unmasks an indomethacin-sensitive (and therefore cyclooxygenase product-mediated) Ang II-induced contraction.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Fulltext Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

Jaarin K, Foong WD, Yeoh MH, Kamarul ZY, Qodriyah HM, Azman A, et al.

Clinics (Sao Paulo), 2015 Nov;70(11):751-7.
PMID: 26602523 DOI: 10.6061/clinics/2015(11)07

This study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers.

Matched MeSH terms: NG-Nitroarginine Methyl Ester
Renoprotective and antihypertensive mechanism of action of Clinacanthus nutans bioactive polysaccharides by suppression of reactive oxygen species/ nuclear factor/ matrix metalloproteinase (ROS/NF-ΚB/MMP-9) and upregulation of endothelial nitric oxide synthase/nitric oxide (eNOS/NO) pathways

Chia TY, Gan CY, Cheah PS, Murugaiyah V, Fatima T, Haji EM, et al.

J Mol Histol, 2025 Jun 28;56(4):209.
PMID: 40580398 DOI: 10.1007/s10735-025-10481-9

Clinacanthus nutans (C. nutans) Lindau, is classified as a top herb which are investigated for different biological activities like antioxidant, anti-inflammatory and vasodilatory effects. Hitherto, no dedicated study has been investigated on the role of C. nutans in L-NAME [N(ω)-nitro-L-arginine methyl ester] in-vivo rat model to explore its antihypertensive and renoprotective mechanism by modulating the ROS/NF-κB/MMP-9 pathways both globally in the plasma as well as locally in the kidney by using in-vitro expression study. Present study hypothesized that bioactive polysaccharides leaves of the alcoholic extract of C. nutans (CNBP) could improve the functions of the kidney by its antioxidant, anti-inflammatory, antihypertensive actions by suppression of ROS/NF-κB/MMP-9 and upregulation of eNOS/NO pathways in the plasma and kidney. Thirty male Sprague-Dawley (SD) rats (n = 6) were randomised into five groups namely: Control (C), L-NAME (L) administered in drinking water, L-NAME + 500 mg/kg of C. nutans bioactive polysaccharides (CNBP) (LCN500), L-NAME + 1000 mg/kg of CNBP (LCN1000) and L-NAME + 2000 mg/kg of CNBP (LCN2000) respectively. All treatments were continued for the period of 14 days and physiological data like water intake, urine output, body weight was collected on days 0, 7 and 14. Acute in-vivo study was performed after cannulation of the femoral and carotid arteries where renal cortical blood perfusion (RCBP) was measured along with pulse wave velocity (PWV). Plasma and renal malondialdehyde (MDA), tumour necrosis factor-α(TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), nitric oxide synthase-1 (NOS1) and superoxide dismutase (SOD) were measured. Histopathological studies were done on the kidney tissue at the termination of experiment. Administrations of L-NAME to L group for 14 days resulted in significantly reduced levels of SOD and NOS while significantly elevated levels of MDA, TNF-α, IL-6 and MMP-9 in both plasma and kidney tissue when compared to control group (C). Conversely, treatment of 500, 1000 and 2000 mg/kg of CNBP has significantly reversed the values when same was compared to normal control ( C) group. Administration of L-NAME to L group for 14 days caused significantly increased systolic blood pressure (SBP) and arterial stiffness by increasing the pulse wave velocity (PWV) along with reduced creatinine clearance and renal cortical blood perfusion (RCBP) when compared to C group. Nevertheless, treatment of 500, 1000 and 2000 mg/kg CNBP has significantly reduced the SBP and PWV and raised the creatine clearance and RCBP functions when compared to (L) group. This study devised with the novel findings of 14 days CNBP treatment has suppressed ROS/TNF-α/MMP-9 pathway in the plasma and kidney which is pathological pathway for the kidney injury and hypertension while upregulated eNOS/NO pathways in plasma and kidney which is renoprotective and antihypertensive pathway in L-NAME rat model of hypertension and kidney injury.

Matched MeSH terms: NG-Nitroarginine Methyl Ester

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links