Displaying publications 1 - 20 of 30 in total

Abstract:
Sort:
  1. Fulltext Interaction between nitric oxide and renal α1-adrenoreceptors mediated vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats
    Ahmad A, Sattar MA, Azam M, Khan SA, Bhatt O, Johns EJ
    PLoS One, 2018;13(2):e0189386.
    PMID: 29447158 DOI: 10.1371/journal.pone.0189386
    Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal α1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal α1-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal α1-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective α1-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione γ lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal α1A, α1B and α1D-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented α1A, α1B and α1D adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/physiology*
  2. Effects of various nonopioid receptor antagonists on the antinociceptive activity of Muntingia calabura extracts in mice
    Zakaria ZA, Hassan MH, Nurul Aqmar MN, Abd Ghani M, Mohd Zaid SN, Sulaiman MR, et al.
    Methods Find Exp Clin Pharmacol, 2007 Oct;29(8):515-20.
    PMID: 18040526
    This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects; Receptors, Adrenergic, alpha-1/metabolism; Receptors, Adrenergic, alpha-2/drug effects; Receptors, Adrenergic, alpha-2/metabolism
  3. Fulltext Influence of combined hypertension and renal failure on functional alpha(1)-adrenoceptor subtypes in the rat kidney
    Hye Khan MA, Sattar MA, Abdullah NA, Johns EJ
    Br J Pharmacol, 2008 Mar;153(6):1232-41.
    PMID: 18246093 DOI: 10.1038/bjp.2008.13
    This study investigated whether the alpha(1)-adrenoceptor responsiveness of the renal vasculature was altered in the state of hypertension combined with renal failure.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects; Receptors, Adrenergic, alpha-1/metabolism*
  4. Regulation of G protein signaling by the 70kDa heat shock protein
    Lim WK, Kanelakis KC, Neubig RR
    Cell Signal, 2013 Feb;25(2):389-96.
    PMID: 23153586 DOI: 10.1016/j.cellsig.2012.11.002
    G protein-coupled receptors (GPCRs) transduce extracellular signals to the interior of the cell by activating membrane-bound guanine nucleotide-binding regulatory proteins (G proteins). An increasing number of proteins have been reported to bind to and regulate GPCRs. We report a novel regulation of the alpha(2A) adrenergic receptor (α(2A)-R) by the ubiquitous stress-inducible 70kDa heat shock protein, hsp70. Hsp70, but not hsp90, attenuated G protein-dependent high affinity agonist binding to the α(2A)-R in Sf9 membranes. Antagonist binding was unchanged, suggesting that hsp70 uncouples G proteins from the receptor. As hsp70 did not bind G proteins but complexed with the α(2A)-R in intact cells, a direct interaction with the receptor seems likely. In the presence of hsp70, α(2A)-R-catalyzed [(35)S]GTPγS binding was reduced by approximately 70%. In contrast, approximately 50-fold higher concentrations of hsp70 were required to reduce agonist binding to the stress-inducible 5-hydroxytryptamine(1A) receptor (5-HT(1A)-R). In heat-stressed CHO cells, the α(2A)-R was significantly uncoupled from G proteins, coincident with an increased localization of hsp70 at the membrane. The contrasting effect of hsp70 on the α(2A)-R compared to the 5-HT(1A)-R suggests that during stress, upregulation of hsp70 may attenuate signaling from specific GPCRs as part of the stress response to foster survival.
    Matched MeSH terms: Receptors, Adrenergic, alpha-2/genetics; Receptors, Adrenergic, alpha-2/metabolism*; Receptors, Adrenergic, alpha-2/chemistry
  5. Special focus on the role of α(1D)-adrenoreceptors in the assessment of renal tubular sodium re-absorptive responses in spontaneously hypertensive rats subjected to high sodium diet
    Kazi RN, Sattar MA, Abdullah NA, Khan MA, Rathore HA, Abdulla MH, et al.
    Yakugaku Zasshi, 2011 Mar;131(3):431-6.
    PMID: 21372540
    α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(₁D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α₁-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(₁D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/physiology*
  6. Association of insertion/deletion polymorphism of alpha-adrenoceptor gene in essential hypertension with or without type 2 diabetes mellitus in Malaysian subjects
    Vasudevan R, Ismail P, Stanslas J, Shamsudin N, Ali AB
    Int J Biol Sci, 2008;4(6):362-7.
    PMID: 18953403
    An insertion/deletion (I/D) polymorphism of Alpha2B-Adrenoceptor (ADRA2B) gene located on chromosome 2 has been studied extensively in related to cardiovascular diseases. The main aim of the present study was to examine the potential association of D allele frequency of I/D polymorphism of ADRA2B gene in Malaysian essential hypertensive subjects with or without type 2 diabetes mellitus (T2DM). This study includes 70 hypertensive subjects without T2DM, 65 hypertensive subjects with T2DM and 75 healthy volunteers as control subjects. Genotyping of I/D polymorphism was performed by conventional PCR method. There was significant difference found in age, body mass index, systolic/diastolic blood pressure and high density lipoprotein cholesterol level between the case and control subjects. DD genotypic frequency of I/D polymorphism was significantly higher in hypertensive subjects (42.84% vs. 29.33%; P-=0.029) and in hypertensive with T2DM subjects (46.15% vs. 29.33%; P=0.046) than control group. D allele frequency was higher in hypertensive group (67.41%) than control subjects (52.67%). However, no significant difference was found between the three genotypes of I/D polymorphism of ADRA2B gene and the clinical characteristics of the subjects. The result obtained in this study show D allele of ADRA2B gene was associated with essential hypertension with or without T2DM in Malaysian subjects.
    Matched MeSH terms: Receptors, Adrenergic, alpha-2/genetics*
  7. Anti-diarrheal activities of phytol along with its possible mechanism of action through in-vivo and in-silico models
    Islam MT, Rahman MA, Saeed M, Ul-Haq Z, Alam MJ, Mondal M, et al.
    Cell Mol Biol (Noisy-le-grand), 2020 Jun 25;66(4):243-249.
    PMID: 32583783
    Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/metabolism; Receptors, Adrenergic, alpha-1/chemistry
  8. Fulltext Biphasic Effects of α-Asarone on Immobility in the Tail Suspension Test: Evidence for the Involvement of the Noradrenergic and Serotonergic Systems in Its Antidepressant-Like Activity
    Chellian R, Pandy V, Mohamed Z
    Front Pharmacol, 2016;7:72.
    PMID: 27065863 DOI: 10.3389/fphar.2016.00072
    Alpha (α)-asarone is one of the main psychoactive compounds, present in Acorus species. Evidence suggests that the α-asarone possess an antidepressant-like activity in mice. However, the exact dose-dependent effect of α-asarone and mechanism(s) involved in the antidepressant-like activity are not clear. The present study aimed to investigate the dose-dependent effect of α-asarone and the underlining mechanism(s) involved in the antidepressant-like activity of α-asarone in the mouse model of tail suspension test (TST). In this study, the acute effect of α-asarone per se at different doses (10-100 mg/kg, i.p.) on immobility in the TST was studied. Additionally, the possible mechanism(s) involved in the antidepressant-like effect of α-asarone was studied using its interaction with noradrenergic and serotonergic neuromodulators in the TST. The present results reveal that the acute treatment of α-asarone elicited biphasic responses on immobility such that the duration of the immobility time is significantly reduced at lower doses (15 and 20 mg/kg, i.p.) but increased at higher doses (50 and 100 mg/kg, i.p.) in the TST. Besides, α-asarone at higher doses (50 and 100 mg/kg, i.p.) significantly decreased the spontaneous locomotor activity. Moreover, pretreatment of mice with noradrenergic neuromodulators such as AMPT (100 mg/kg, i.p., a catecholamine synthesis inhibitor), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist) and with serotonergic neuromodulators such as PCPA (100 mg/kg, i.p., once daily for four consecutive days, a serotonin synthesis inhibitor,) and WAY100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist) significantly reversed the anti-immobility effect of α-asarone (20 mg/kg, i.p.). Taken together, our results suggest that the acute treatment with α-asarone elicited biphasic actions in the TST in which antidepressant-like effect was seen at relatively lower doses (15 and 20 mg/kg, i.p.) and depressive-like activity at relatively higher doses (50 and 100 mg/kg, i.p.). Furthermore, it has been revealed that the antidepressant-like effect of α-asarone could be mediated through both noradrenergic (α1 and α2 adrenoceptors) and serotonergic (particularly, 5-HT1A receptors) systems.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1
  9. Fulltext Claustrophobia in MRI: is there a role for dexmedetomidine? An observational case series study involving 11 patients
    Rai, V., Norhasayani, T., Chan, L.
    JUMMEC, 2013;16(1):1-4.
    MyJurnal
    MRI can be a distressing and traumatic experience in many patients, especially in those with underlying anxiety and/or claustrophobia. We conducted a study to determine if dexmedetomidine as a sedative agent can alleviate these symptoms. Dexmedetomidine is a potent and highly selective α-2 adrenergic receptor agonist which has sedative and analgesic properties. Eleven adult patients (n=11) with a histroy of anxiety and/or claustrophobia undergoing MRI who expressed their desire for sedation were recruited. Dexmedetomidine was infused at 0.5 to 1.0 μg/kg over 10 minutes prior to scanning. Eight patients (n=8) were able to complete the MRI scan comfortably. The findings suggest that dexmedetomidine provides adequate sedation that can allow patients with anxiety and/or claustrophobia to undergo MRI scanning succesfully in a large poproption of the population with anxiety. This result however is still preliminary and will need to be validated in a more robust clinical study.
    Matched MeSH terms: Receptors, Adrenergic, alpha-2
  10. In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT2 and α1 receptors
    Heng HL, Chee CF, Thy CK, Tee JT, Chin SP, Herr DR, et al.
    Chem Biol Drug Des, 2019 02;93(2):132-138.
    PMID: 30216681 DOI: 10.1111/cbdd.13390
    Compounds with activity at serotonin (5-hydroxytryptamine) 5-HT2 and α1 adrenergic receptors have potential for the treatment of central nervous system disorders, drug addiction or overdose. Isolaureline, dicentrine and glaucine enantiomers were synthesized, and their in vitro functional activities at human 5-HT2 and adrenergic α1 receptor subtypes were evaluated. The enantiomers of isolaureline and dicentrine acted as antagonists at 5-HT2 and α1 receptors with (R)-isolaureline showing the greatest potency (pKb  = 8.14 at the 5-HT2C receptor). Both (R)- and (S)-glaucine also antagonized α1 receptors, but they behaved very differently to the other compounds at 5-HT2 receptors: (S)-glaucine acted as a partial agonist at all three 5-HT2 receptor subtypes, whereas (R)-glaucine appeared to act as a positive allosteric modulator at the 5-HT2A receptor.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/genetics; Receptors, Adrenergic, alpha-1/metabolism*; Receptors, Adrenergic, alpha-1/chemistry
  11. High-fructose feeding impacts on the adrenergic control of renal haemodynamics in the rat
    Abdulla MH, Sattar MA, Johns EJ, Abdullah NA, Hye Khan MA, Rathore HA
    Br J Nutr, 2012 Jan;107(2):218-28.
    PMID: 21733307 DOI: 10.1017/S0007114511002716
    The present study explored the hypothesis that a prolonged 8 weeks exposure to a high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated vasoconstriction and is associated with a higher contribution of α1D-adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 % fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8 weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined in the presence and absence of BMY7378 (α1D-adrenoceptor antagonist). FFR had increased blood pressure, plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang II: 54 %). Furthermore in the C group, the magnitude of the renal cortical vasoconstriction to all agonists was blunted in the presence of the low or high dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53 and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and 177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the α1D-adrenoceptor subtype results in enhancement of renal vasoconstriction to adrenergic agonists, suggesting an inhibitory action of α1D-adrenoceptors in the FFR. α1D-Adrenoceptors buffer the AT1-receptor response in the renal vasculature of normal rats and fructose feeding suppressed this interaction.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/metabolism*; Receptors, Adrenergic, alpha-1/chemistry
  12. Evidence for the role of α1A-adrenoceptor subtype in the control of renal haemodynamics in fructose-fed Sprague-Dawley rat
    Abdulla MH, Sattar MA, Johns EJ, Abdullah NA, Khan MA
    Eur J Nutr, 2011 Dec;50(8):689-97.
    PMID: 21373947 DOI: 10.1007/s00394-011-0180-9
    AIM: To explore the hypothesis that high fructose intake results in a higher functional contribution of α1A-adrenoceptors and blunts the adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction.

    METHODS: Twelve Sprague-Dawley rats received either 20% fructose solution [FFR] or tap water [C] to drink ad libitum for 8 weeks. The renal vasoconstrictor response to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II was determined in the presence and absence of 5-methylurapidil (5-MU) (α1A-adrenoceptor antagonist) in a three-phase experiment (pre-drug, low- and high-dose 5-MU). Data, mean ± SEM were analysed by ANOVA or Student's unpaired t-test with significance at P < 0.05.

    RESULTS: FFR exhibited insulin resistance (HOMA index), hypertension and significant increases in plasma levels of glucose and insulin. All agonists caused dose-related reductions in cortical blood perfusion that were larger in C than in FFR while the magnitudes of the responses were progressively reduced with increasing doses of 5-MU in both C and FFR. The degree of 5-MU attenuation of the renal cortical vasoconstriction due to NA, ME and Ang II was significantly greater in the FFR compared to C.

    CONCLUSIONS: Fructose intake for 8 weeks results in smaller vascular response to adrenergic agonists and Ang II. The α1A-adrenoceptor subtype is the functional subtype that mediates renal cortical vasoconstriction in control rats, and this contribution becomes higher due to fructose feeding.

    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects*; Receptors, Adrenergic, alpha-1/metabolism*
  13. Influence of high dietary sodium intake on the functional subtypes of alpha-adrenoceptors in the renal cortical vasculature of Wistar-Kyoto rats
    Kazi RN, Munavvar AS, Abdullah NA, Khan AH, Johns EJ
    Auton Autacoid Pharmacol, 2009 Jan;29(1-2):25-31.
    PMID: 19302553 DOI: 10.1111/j.1474-8673.2009.00428.x
    1 Increased renal vascular resistance is one renal functional abnormality that contributes to hypertension, and alpha(1)-adrenoceptors play a pivotal role in modulating this renal vascular resistance. This study investigates the functional contribution of alpha(1)-adrenoceptor subtypes in the renal cortical vasculature of Wistar-Kyoto rats on a normal sodium diet (WKYNNa) compared with those given saline to drink for 6 weeks (WKYHNa). 2 The renal cortical vascular responses to the adrenergic agonists noradrenaline (NA), methoxamine (ME) and phenylephrine (PE) were measured in WKYHNa and WKYNNa rats either in the absence (the control phase) or presence of chloroethylclonidine (CEC), an alpha(1B)-adrenoceptor antagonist, 5-methylurapidil (5-MeU), an alpha(1A) antagonist, or BMY7378, an alpha(1D) antagonist. 3 Results showed a greater renal cortical vascular sensitivity to NA, PE and ME in the WKYHNa compared with WKYNNa rats (P < 0.05). Moreover, 5-MeU and BMY7378 attenuated adrenergically induced renal cortical vasoconstriction in WKYHNa and WKYNNa rats; this response was largely blunted in CEC-treated WKYHNa rats (all P < 0.05) but not in CEC-treated WKYNNa rats. 4 The data suggest that irrespective of dietary sodium content, in Wistar-Kyoto rats alpha(1A)- and alpha(1D)-subtypes are the major alpha(1)-adrenoceptors in renal cortical vasculature; however, there appears to be a functional involvement of alpha(1B)-adrenoceptors in the WKYHNa rats.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects*; Receptors, Adrenergic, alpha-1/physiology*
  14. Alpha1A- and alpha1D-adrenoceptors are the major functional subtypes of renal alpha1-adrenoceptors in streptozotocin-induced diabetic and normal Sprague-Dawley rats
    Armenia, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Auton Autacoid Pharmacol, 2008 Jan;28(1):1-10.
    PMID: 18257746 DOI: 10.1111/j.1474-8673.2007.00412.x
    1 The present study investigated the effect of streptozotocin-induced diabetes on alpha(1)-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly (P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant (P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional alpha-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of alpha(1B)-adrenoceptor subtypes in non-diabetic SD rats.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects; Receptors, Adrenergic, alpha-1/metabolism*
  15. Cisplatin-induced nephrotoxicity causes altered renal hemodynamics in Wistar Kyoto and spontaneously hypertensive rats: role of augmented renal alpha-adrenergic responsiveness
    Hye Khan MA, Abdul Sattar M, Abdullah NA, Johns EJ
    Exp. Toxicol. Pathol., 2007 Nov;59(3-4):253-60.
    PMID: 17764917
    The pathogenesis of cisplatin-induced renal failure is related to reduced renal blood flow due to severe tubular damage and enhanced renovascular resistance. It is also known that alpha(1)-adrenoceptors, the major subtype of alpha-adrenoceptors in renal vasculature play the pivotal role in regulating renal hemodynamics. With this background, we have hypothesized that the altered renal hemodynamics and enhanced renovascular resistance in cisplatin-induced renal failure might be caused by the altered alpha-adrenergic responsiveness with a possible involvement of alpha(1)-adrenoceptors in the renal vasculature. In a unique experimental approach with anesthetized rats, this study has therefore examined if there is any shift in the renovascular responsiveness to renal nerve stimulation and a series of alpha-adrenergic agonists in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats with cisplatin-induced renal failure in comparison with their body weight-matched normal controls. Thirty-two male rats of both WKY (n=16) and SHR (n=16) origin with body weight 236+/-7.9 g received cisplatin (5mg/kg i.p.). The renal failure was confirmed in terms of significantly reduced renal blood flow, reduced creatinine clearance, increased fractional excretion of sodium, increased kidney index (all P<0.05) and tubular damage. After 7 days of cisplatin, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The changes in the vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by electrical renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine and methoxamine. It was observed that in the cisplatin-treated renal failure WKY and SHR rats there were significant (all P<0.05) reductions in the renal blood flow along with significantly (P<0.05) higher renal adrenergic responsiveness as compared with their non-renal failure controls. The data showed that in the renal failure WKY and SHR rats, the altered renal hemodynamics might be caused by an augmented renal adrenergic responsiveness. The results obtained further led us to suggest that the augmented renal adrenergic responsiveness in the cisplatin-induced renal failure rats were possibly mediated by the alpha(1)-adrenoceptors.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/drug effects*; Receptors, Adrenergic, alpha-1/metabolism
  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 alpha adrenoceptors, and ANGII in the renal vasculature of the SHR.
    Matched MeSH terms: Receptors, Adrenergic, alpha/genetics; Receptors, Adrenergic, alpha/metabolism
  17. Functional subtypes of renal alpha1-adrenoceptor in spontaneously hypertensive rats with streptozotocin-induced experimental diabetic nephropathy
    Khan MA, Sattar MA, Abdullah NA, Abdulla MH, Salman IM, Kazi RN, et al.
    Kidney Blood Press Res, 2009;32(5):349-59.
    PMID: 19844130 DOI: 10.1159/000249149
    This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/classification*; Receptors, Adrenergic, alpha-1/metabolism*
  18. Association of ADRA2A and MTHFR gene polymorphisms with weight loss following antipsychotic switching to aripiprazole or ziprasidone
    Roffeei SN, Reynolds GP, Zainal NZ, Said MA, Hatim A, Aida SA, et al.
    Hum Psychopharmacol, 2014 Jan;29(1):38-45.
    PMID: 24424705 DOI: 10.1002/hup.2366
    Various genetic polymorphisms have been reported to be associated with antipsychotic-induced weight gain. In this study, we aimed to determine whether risk polymorphisms in 12 candidate genes are associated with reduction in body mass index (BMI) of patients following switching of antipsychotics to aripiprazole or ziprasidone.
    Matched MeSH terms: Receptors, Adrenergic, alpha-2/genetics*
  19. Fulltext Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats
    Abdulla MH, Sattar MA, Abdullah NA, Khan AH, Anand Swarup KR, Rathore HA, et al.
    Ups. J. Med. Sci., 2011 Mar;116(1):18-25.
    PMID: 21047287 DOI: 10.3109/03009734.2010.526723
    This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats.
    Matched MeSH terms: Receptors, Adrenergic, alpha-1/physiology
  20. Fulltext Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy
    Ahmad A, Sattar MA, Azam M, Abdulla MH, Khan SA, Hashmi F, et al.
    PLoS One, 2016;11(5):e0154995.
    PMID: 27191852 DOI: 10.1371/journal.pone.0154995
    The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development.
    Matched MeSH terms: Receptors, Adrenergic, alpha/metabolism*
Related Terms
Filters
Contact Us

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

External Links