Displaying publications 41 - 60 of 65 in total

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  1. The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats
    Chia TY, Sattar MA, Abdulla MH, Rathore HA, Ahmad Fu, Kaur G, et al.
    Ren Fail, 2013 Aug;35(7):978-88.
    PMID: 23822648 DOI: 10.3109/0886022X.2013.809563
    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p 
  2. 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.
  3. Renal ischemic injury affects renal hemodynamics and excretory functions in Sprague Dawley rats: involvement of renal sympathetic tone
    Salman IM, Sattar MA, Abdullah NA, Ameer OZ, Yam MF, Kaur G, et al.
    Ren Fail, 2010 Jan;32(1):96-102.
    PMID: 20113274 DOI: 10.3109/08860220903389196
    The role of renal sympathetic nerves in the pathogenesis of ischemic acute renal failure (ARF) and the immediate changes in the renal excretory functions following renal ischemia were investigated. Two groups of male Sprague Dawley (SD) rats were anesthetized (pentobarbitone sodium, 60 mg kg(-1) i.p.) and subjected to unilateral renal ischemia by clamping the left renal artery for 30 min followed by reperfusion. In group 1, the renal nerves were electrically stimulated and the responses in the renal blood flow (RBF) and renal vascular resistance (RVR) were recorded, while group 2 was used to study the early changes in the renal functions following renal ischemia. In post-ischemic animals, basal RBF and the renal vasoconstrictor reperfusion to renal nerve stimulation (RNS) were significantly lower (all p < 0.05 vs. control). Mean arterial pressure (MAP), basal RVR, urine flow rate (UFR), absolute and fractional excretions of sodium (U(Na)V and FE(Na)), and potassium (U(K)V and FE(K)) were higher in ARF rats (all p < 0.05 vs. control). Post-ischemic animals showed markedly lower glomerular filtration rate (GFR) (p < 0.05 vs. control). No appreciable differences were observed in urinary sodium to potassium ratio (U(Na)/U(K)) during the early reperfusion phase of renal ischemia (p > 0.05 vs. control). The data suggest an immediate involvement of renal sympathetic nerve action in the pathogenesis of ischemic ARF primarily through altered renal hemodynamics. Diuresis, natriuresis, and kaliuresis due to impaired renal tubular functions are typical responses to renal ischemia and of comparable magnitudes.
  4. Inhibition of Ang II and renal sympathetic nerve influence dopamine-and isoprenaline-induced renal haemodynamic changes in normal Wistar-Kyoto and spontaneously hypertensive rats
    Abdulla MH, Sattar MA, Abdullah NA, Hazim AI, Anand Swarup KR, Rathore HA, et al.
    Auton Autacoid Pharmacol, 2008 Oct;28(4):95-101.
    PMID: 18778332 DOI: 10.1111/j.1474-8673.2008.00422.x
    1. This study was undertaken to elucidate the effects of inhibiting the renin-angiotensin system (RAS) with losartan, and acute unilateral renal denervation on renal haemodynamic responses to intrarenal administration of vasoconstrictor doses of dopamine and vasodilator doses of isoprenaline in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2. Acute unilateral renal denervation of the left kidney in rats was confirmed by a drop in the renal vasoconstrictor response to renal nerve stimulation (P < 0.05) along with diuresis and natriuresis. Rats were pretreated with losartan for 7 days and thereafter animals fasted overnight were anaesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and acute renal haemodynamic responses studied. 3. Dose-response curves were constructed for dopamine and isoprenaline that induced falls or increases in renal blood flow, respectively. It was observed that renal vascular responses were greater in the denervated as compared with rats with intact renal nerves (all P < 0.05). Dopamine-induced renal vasoconstrictor responses were markedly lower in losartan-treated denervated WKY and SHR compared with their untreated counterparts (all P < 0.05). It was also observed that in losartan-treated and denervated WKY rats the vasodilatory responses to isoprenaline were markedly lower compared with untreated rats (all P < 0.05). However, in SHR, under the same conditions, there was no difference in the renal response to isoprenaline whether or not rats were treated with losartan (P > 0.05). 4. The data obtained showed that the renal vasoconstrictor effect of dopamine depends on intact renal nerves and RAS in WKY and SHR. Isoprenaline responses were likewise sensitive to renal denervation and RAS inhibition in WKY rats but not SHRs. Our observations reveal a possible relationship between renal AT(1) receptors and alpha(1)-adrenoceptors in WKY and SHR. There is also evidence to suggest an interaction between renal beta-adrenoceptors and AT(1) receptors in WKY rats.
  5. Blunted endogenous GABA-mediated inhibition in the hypothalamic paraventricular nucleus of rats with streptozotocin-induced diabetes
    Hassan Z, Sattar MZ, Suhaimi FW, Yusoff NH, Abdulla MH, Yusof AP, et al.
    Acta Neurol Belg, 2013 Sep;113(3):319-25.
    PMID: 23242937 DOI: 10.1007/s13760-012-0165-3
    The hypothalamic paraventricular nucleus (PVN) is involved in the regulation of sympathetic outflow and particularly affects the heart. This study sets out to determine the role of GABA of the paraventricular nucleus (PVN) in cardiovascular regulation in streptozotocin-induced diabetic rats. Pharmacological stimulation of glutamatergic receptors with DL-Homocysteic acid (200 mM in 100 nL) in the PVN region showed a significant depression in both mean arterial pressure (MAP) and heart rate (HR) of diabetic rats (Diabetic vs. non-diabetic: MAP 15.0 ± 1.5 vs. 35.8 ± 2.8 mmHg; HR 3.0 ± 2.0 vs. 30.0 ± 6.0 bpm, P < 0.05). Microinjection of bicuculline methiodide (1 mM in 100 nL), a GABAA receptor antagonist, produced an increase in baseline MAP and HR in both non-diabetic and diabetic rats. In the diabetic rats, bicuculline injection into the PVN reduced the pressor and HR responses (Diabetic vs. non-diabetic: MAP 6.2 ± 0.8 vs. 25.1 ± 2.2 mmHg; HR 1.8 ± 1.1 vs. 25.4 ± 6.2 bpm, P < 0.05). A microinjection of muscimol (2 mM in 100 nL), which is a GABAA receptor agonist, in the PVN elicited decreases in MAP and HR in both groups. The diabetic group showed a significantly blunted reduction in HR, but not MAP (Diabetic vs. non-diabetic: MAP -15.7 ± 4.0 vs. -25.0 ± 3.8 mmHg; HR -5.2 ± 2.1 vs. -39.1 ± 7.9 bpm). The blunted vasopressor and tachycardic responses to bicuculline microinjection in the diabetic rats are likely to result from decreased GABAergic inputs, attenuated release of endogenous GABA or alterations in GABAA receptors within the PVN.
  6. 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.
  7. Fulltext Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats
    Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, et al.
    J Inflamm Res, 2021;14:689-710.
    PMID: 33716510 DOI: 10.2147/JIR.S299083
    Purpose: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver.

    Methods: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies.

    Results: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD.

    Conclusion: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.

  8. Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar-Kyoto rats
    Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Abdullah NA, et al.
    Can J Physiol Pharmacol, 2014 Dec;92(12):1029-35.
    PMID: 25403946 DOI: 10.1139/cjpp-2014-0236
    This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg · (kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg · L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.
  9. Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions
    Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, et al.
    Pathology, 2010 Apr;42(3):259-66.
    PMID: 20350220 DOI: 10.3109/00313021003631304
    We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury.
  10. Renal sympathetic nervous system hyperactivity in early streptozotocin-induced diabetic kidney disease
    Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Abdullah GZ, et al.
    Neurourol Urodyn, 2011 Mar;30(3):438-46.
    PMID: 21284025 DOI: 10.1002/nau.21007
    We assessed the role of renal sympathetic nervous system in the deterioration of renal hemodynamic and excretory functions in rats with streptozotocin (STZ)-induced diabetic kidney disease (DKD).
  11. Inhibition of L-NAME-induced hypertension by combined treatment with apocynin and catalase: the role of Nox 4 expression
    Chia TY, Murugaiyah V, Khan NA, Sattar MA, Abdulla MH, Johns EJ, et al.
    Physiol Res, 2021 03 17;70(1):13-26.
    PMID: 33728924
    Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.
  12. The restorative effect of apocynin and catalase in l-arginine induced hypotension on normotensive subjects - the role of oxidative stress
    Chia TY, Murugaiyah V, Sattar MA, Khan NAK, Ahmad A, Abdulla MH, et al.
    Physiol Res, 2020 12 22;69(6):1051-1066.
    PMID: 33210935
    L-arginine is a substrate for nitric oxide synthase (NOS) responsible for the production of NO. This investigation studied the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on L-arginine induced oxidative stress and hypotension. Forty Wistar-Kyoto rats were treated for 14 days with vehicle, L-arginine (12.5mg/ml p.o.), L-arginine+apocynin (2.5mmol/L p.o.), L-arginine+catalase (10000U/kg/day i.p.) and L-arginine plus apocynin+catalase respectively. Weekly renal functional and hemodynamic parameters were measured and kidneys harvested at the end of the study for histopathological and renal NADPH oxidase 4 (Nox4) assessments. L-arginine administration in normotensive rats decreased systolic blood pressure (120±2 vs 91±2mmHg) and heart rate (298±21 vs 254±15b/min), enhanced urinary output (21.5±4.2 vs 32±1.9ml/24h , increased creatinine clearance (1.72±0.56 vs 2.62±0.40ml/min/kg), and fractional sodium excretion (0.88±0.16 vs 1.18±0.16 %), caused proteinuria (28.10±1.93 vs 35.26±1.69mg/kg/day) and a significant decrease in renal cortical blood perfusion (292±3 vs 258±5bpu) and pulse wave velocity (3.72±0.20 vs 2.84±0.13m/s) (all P<0.05). L-arginine increased plasma malondialdehyde (by ~206 % P<0.05) and NO (by~51 %, P<0.05) but decreased superoxide dismutase (by~31 %, P<0.05) and total antioxidant capacity (by~35 %, P<0.05) compared to control. Renal Nox4 mRNA activity was approximately 2.1 fold higher (P<0.05) in the L-arginine treated rats but was normalized by apocynin and apocynin plus catalase treatment. Administration of apocynin and catalase, but not catalase alone to rats fed L-arginine, restored the deranged renal function and structure, prevented hypotension and enhanced the antioxidant capacity and suppressed Nox4 expression. These findings suggest that apocynin and catalase might be used prophylactically in states of oxidative stress.
  13. Fulltext Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats
    Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Azam M, et al.
    PLoS One, 2016;11(3):e0150137.
    PMID: 26963622 DOI: 10.1371/journal.pone.0150137
    Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05) in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05) in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05) plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II) and noradrenaline (NA) but attenuates oxidative stress and improves pulse wave velocity which helps to suppress LVH. Exogenous administration of H2S augmented the reduced renal cortical blood perfusion in the LVH state.
  14. Fulltext A critical review of pharmacological significance of Hydrogen Sulfide in hypertension
    Ahmad A, Sattar MA, Rathore HA, Khan SA, Lazhari MI, Afzal S, et al.
    Indian J Pharmacol, 2015 May-Jun;47(3):243-7.
    PMID: 26069359 DOI: 10.4103/0253-7613.157106
    In the family of gas transmitters, hydrogen sulfide (H2S) is yet not adequately researched. Known for its rotten egg smell and adverse effects on the brain, lungs, and kidneys for more than 300 years, the vasorelaxant effects of H2S on blood vessel was first observed in 1997. Since then, research continued to explore the possible therapeutic effects of H2S in hypertension, inflammation, pancreatitis, different types of shock, diabetes, and heart failure. However, a considerable amount of efforts are yet needed to elucidate the mechanisms involved in the therapeutic effects of H2S, such as nitric oxide-dependent or independent vasodilation in hypertension and regression of left ventricular hypertrophy. More than a decade of good repute among researchers, H2S research has certain results that need to be clarified or reevaluated. H2S produces its response by multiple modes of action, such as opening the ATP-sensitive potassium channel, angiotensin-converting enzyme inhibition, and calcium channel blockade. H2S is endogenously produced from two sulfur-containing amino acids L-cysteine and L-methionine by the two enzymes cystathionine γ lyase and cystathionine β synthase. Recently, the third enzyme, 3-mercaptopyruvate sulfur transferase, along with cysteine aminotransferase, which is similar to aspartate aminotransferase, has been found to produce H2S in the brain. The H2S has interested researchers, and a great deal of information is being generated every year. This review aims to provide an update on the developments in the research of H2S in hypertension amid the ambiguity in defining the exact role of H2S in hypertension because of insufficient number of research results on this area. This critical review on the role of H2S in hypertension will clarify the gray areas and highlight its future prospects.
  15. Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats
    Salman IM, Sattar MA, Ameer OZ, Abdullah NA, Yam MF, Salman HM, et al.
    Indian J Med Res, 2010 Jun;131:786-92.
    PMID: 20571167
    A wealth of information concerning the essential role of renal sympathetic nerve activity (RSNA) in the regulation of renal function and mean arterial blood pressure homeostasis has been established. However, many important parameters with which RSNA interacts are yet to be explicitly characterized. Therefore, the present study aimed to investigate the impact of acute renal denervation (ARD) on sodium and water excretory responses to intravenous (iv) infusions of either norepinephrine (NE) or angiotensin II (Ang II) in anaesthetized spontaneously hypertensive rats (SHR).
  16. Fulltext Effect of dragon fruit extract on oxidative stress and aortic stiffness in streptozotocin-induced diabetes in rats
    Anand Swarup KR, Sattar MA, Abdullah NA, Abdulla MH, Salman IM, Rathore HA, et al.
    Pharmacognosy Res, 2010 Jan;2(1):31-5.
    PMID: 21808536 DOI: 10.4103/0974-8490.60582
    Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats.
  17. 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.
  18. Role of renal sympathetic nervous system in the control of renal potassium handling
    Salman IM, Sattar MA, Abdullah NA, Ameer OZ, Basri F, Hussain NM, et al.
    J Nephrol, 2010 May-Jun;23(3):291-6.
    PMID: 20349424
    It is well established that renal sympathetic nerves are primarily involved in renal sodium and water regulation. However, the relationship between renal sympathetic nerve activity (RSNA) and renal potassium handling is not extensively known. The present study was performed to investigate the role of the renal sympathetic nervous system in the regulation of tubular potassium reabsorption and secretion.
  19. Interaction between renin-angiotensin and sympathetic nervous systems in a rat model of pressure overload cardiac hypertrophy
    Rathore HA, Munavvar AS, Abdullah NA, Khan AH, Fathihah B, NurJannah MH, et al.
    Auton Autacoid Pharmacol, 2009 Oct;29(4):171-80.
    PMID: 19740088 DOI: 10.1111/j.1474-8665.2009.00445.x
    1 A raised cardiac workload activates neurohormones which will increase muscle mass and shift contractility to the right along the Frank-Starling curve. 2 This study examined the interaction between the SNS and RAS in contributing to vascular responsiveness following the development of cardiac hypertrophy due to aortic banding. 3 Sprague Dawley rats (180-200 g) were assigned to one of six groups; Normal, Sham-operated, Aortic Banded (AB), Aortic Banded treated with losartan (ABLOS), Aortic Banded treated with 6-hydroxydopamine (ABSYMP) and Aortic banded treated with both losartan and 6-hydroxydopamine (ABSYMPLOS). A constricting band was placed around the supra renal aorta on day zero with drug treatment from day 37 to day 44. Vasopressor responses to noradrenaline, phenylephrine, methoxamine and angiotensin II were measured on day 45. 4 The magnitudes of the MAP responses to all vasoactive agents, expressed as percentage changes, were similar in Normal and Sham groups, but reduced in the AB group. ABLOS group showed attenuated response to ANGII whereas all responses were enhanced in the ABSYM group. 5 A positive interaction between the two systems was observed with alpha(1A)-adrenoceptors identified as a major component of SNS and AT(1) receptors of RAS to induce vasopressor effects.
  20. Fulltext Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats
    Tan YC, Abdul Sattar M, Ahmeda AF, Abdul Karim Khan N, Murugaiyah V, Ahmad A, et al.
    PLoS One, 2020;15(4):e0231472.
    PMID: 32298299 DOI: 10.1371/journal.pone.0231472
    Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P<0.05) compared to control. CsA increased blood pressure (by 46mmHg) and decreased creatinine clearance (by 49%, all P<0.05). Treatment of CsA rats with apocynin, catalase, and their combination decreased blood pressure to near control values (all P<0.05). NOX4 mRNA activity was higher in the renal tissue of CsA rats by approximately 63% (P<0.05) compared to controls but was reduced in apocynin (by 64%), catalase (by 33%) and combined treatment with apocynin and catalase (by 84%) compared to untreated CsA rats. Treatment of CsA rats with apocynin, catalase, and their combination prevented hypertension and restored renal functional parameters and tissue Nox4 expression in this model. NADPH inhibition and H2O2 scavenging is an important therapeutic strategy during CsA nephrotoxicity and hypertension.
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