Papers by Mohammed H. Abdulla
PloS one, 2016
The purpose of the present study was to investigate the interaction between H2S and NO (nitric ox... more 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<...
Proceedings of the Physiological Society, Jul 3, 2012
ABSTRACT The low-pressure baroreceptors are sensitive to circulatory volume and initiate a reflex... more ABSTRACT The low-pressure baroreceptors are sensitive to circulatory volume and initiate a reflex renal sympatho-excitation or inhibition. This study investigated the contribution of NO to low pressure baroreceptor regulation of RSNA and whether there was a role for AT2 receptors. Groups of Wistar rats (275-350g) were anaesthetised with 1ml chloralose/urethane mixture (16.5/250mg/ml) IP. Cannulae were inserted into the right femoral artery, for mean arterial pressure (MAP) and heart rate (HR) measurement, and vein for saline (NaCl, 9g/L) infusion and supplementary anaesthetic. A cannula was placed in the right intracerebroventricle (ICV) for infusion of drugs. The left kidney was exposed, a renal sympathetic nerve dissected and sealed onto recording electrodes. Saline was infused ICV at 30µl/h for 10min followed by a maintenance infusion of 7.5µl/h for 30min after which the first volume expansion was performed by infusing saline at 0.25% bwt/min IV for 30min. Thereafter, the ICV infusion was switched to either PD123319 (PD, 50µg/kg/min), an AT2 receptor antagonist (n=6) or L-NAME (LNM, 150µg/kg/min), a NO synthase inhibitor (n=8) after which a second volume expansion was performed. Another group of rats received ICV PD or LNM initially followed by PD+LNM as combination (n=6 and 7, respectively). Baseline MAP, HR and RSNA were recorded for 5 min before starting the first and second volume expansion. Data, mean±SEM were analysed using the Student&#39;s t-test with significance at P&lt;0.05. Animals were killed with an anaesthetic overdose. MAP, HR and RSNA following either PD (75±6mmHg, 319±20bpm, 0.69±0.17µV.s) or LNM (82±7mmHg, 304±14bpm, 0.95±0.33µV.s) were not different from those following saline infusion (67±4mmHg, 307±15bpm, 0.82±0.17µV.s; 77±6mmHg, 312±16bpm, 1.00±0.1µV.s respectively). MAP was increased after ICV PD+LNM compared to either PD or LNM (PD+LNM vs. PD, 77±5 vs. 64±7mmHg and PD+LNM vs. LNM 89±5 vs. 80±4mmHg; both P&lt;0.05). Volume expansion decreased RSNA in all groups by some 64±10% (P&lt;0.05) at the end of the 30min. Infusion of PD ICV had no effect on the magnitude of the renal sympatho-inhibition. Following ICV LNM, the reduction in RSNA was less compared to that obtained during saline infusion (46±11 vs. 64±10%, P&lt;0.05, respectively). Similarly, in the PD+LNM group where PD preceded LNM, the fall in RSNA was smaller than when PD was infused alone (37±8 vs. 63±7%, P&lt;0.05, respectively) but not if PD was given after the LNM. These findings suggest that NO is important in allowing the normal renal sympatho-inhibition to occur in response to a volume load but that AT2 receptors do not contribute to this reflex mechanism.
PloS one, 2016
Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role... more 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 veloc...
The current study evaluates the impact of high saturated fat feeding in rat model of gentamicin i... more The current study evaluates the impact of high saturated fat feeding in rat model of gentamicin induced nephrotoxicity on renal function. Sprague-Dawley rats weighing 150-250 gm were randomized into four groups viz (control), (HFD); fed a high fat diet rich in palm kernel oil (40% of Calories as fat) for 8 weeks, (HFDG); fed as HFD and injected with 80 mg/kg (body weight)/day gentamicin intraperitoneally during the last 24 days of the feeding period and IV (G); fed standard chow diet and injected gentamicin as mentioned above. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent surgical procedure for hemodynamic parameters measurement. Then both kidneys were excised for performing a histology study and measuring malonyldialdehyde (a marker of oxidative stress) level in renal homogenate. The results divulged sturdier nephrotoxicity for the group fed with saturated fat; as it was graded as moderate in HFDG group and mild for G group. Overall, changing of feeding behavior toward using more SAFFAs promotes the progression of renal failure.
The Faseb Journal, Apr 1, 2010
Pakistan Journal of Pharmaceutical Sciences, Jul 1, 2013
Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II (Ang II) and... more Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of high-fructose-fed rat. Twenty-four Sprague-Dawley (SD) rats were fed for 8 weeks either 20% fructose solution (FFR) or tap water (C) ad libitum. FFR or C group received losartan (10mg/kg/day p.o.) for 1 week at the end of feeding period (FFR-L and L) respectively, then the vasopressor responses to Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. The responses (%) to NA, PE, ME and Ang II in FFR were lower (P<0.05) than C (FFR vs. C; 22±2 vs. 32±2, 30±3 vs. 40±3, 9±1 vs. 13±1, 10±1 vs. 17±1) respectively. L group had blunted (P<0.05) responses to NA, PE, ME and Ang II compared to C (L vs. C; 26±2 vs. 32±2, 30±3 vs. 40±3, 7±0.7 vs. 13±1, 5±0.4 vs. 17±1) respectively. FFR-L group had aggravated (P<0.05) response to NA and ME, but blunted response to Ang II compared to FFR (FFR-L vs. FFR; 39±3 vs. 22±2, 11±1 vs. 9±1, 3±0.4 vs. 10±1) respectively. Fructose intake for 8 weeks results in smaller vasopressor response to adrenergic agonists and Ang II. Data also demonstrated an important role played by Ang II in the control of systemic haemodynamics in FFR and point to its interaction with adrenergic neurotransmission.
Nitric oxide (NO) interacts with the local brain renin-angiotensin system to modulate sympathetic... more Nitric oxide (NO) interacts with the local brain renin-angiotensin system to modulate sympathetic outflow and cardiovascular homoeostasis. This study investigated whether NO influenced the ability of angiotensin AT2 receptor activation to modify the high-pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR). Anaesthetized (chloralose/urethane) rats were prepared to allow generation of baroreflex gain curves for RSNA or HR following intracerebroventricular (I.C.V.) CGP42112 (AT2 receptor agonist), PD123319 (AT2 receptor antagonist) or losartan (AT1 receptor antagonist), and then in combination with L-NAME (NO synthase inhibitor). I.C.V. PD123319, CGP42112, and Losartan did not change baseline mean arterial pressure, HR or RSNA. Baroreflex sensitivities for RSNA and HR were increased following AT2 receptor activation with CGP42112 by 112 and 157%, respectively, but were reduced following PD123319 by 20% (all P &lt; 0.05). L-NAME alone increased baroreflex sensitivity for both RSNA and HR, by 62 and 158%, respectively, but when co-infused with either CGP42112 or PD123319, the baroreflex sensitivity fell to values comparable to those obtained during I.C.V. saline infusion. The baroreflex sensitivities for RSNA and HR were increased by losartan by 92% and 192%, respectively, but in the presence of L-NAME were no different from those obtained during I.C.V. saline infusion. There is an important facilitatory role for AT2 receptors in the high-pressure baroreflex regulation of RSNA and HR which is dependent on a functional NO/NOS system. Conversely, AT1 receptors have an inhibitory effect on the baroreflex, an action that relies on a tonic inhibition of NO.
Applied Physiology, Nutrition, and Metabolism, 2015
This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstr... more This study investigated the effect of tempol (a superoxide dismutase mimetic) on renal vasoconstrictor responses to angiotensin II (Ang II) and adrenergic agonists in fructose-fed Sprague-Dawley rats (a model of metabolic syndrome). Rats were fed 20% fructose in drinking water (F) for 8 weeks. One fructose-fed group received tempol (FT) at 1 mmol·L(-1) in drinking water for 8 weeks or as an infusion (1.5 mg·kg(-1)·min(-1)) intrarenally. At the end of the treatment regimen, the renal responses to noradrenaline, phenylephrine, methoxamine, and Ang II were determined. F rats exhibited hyperinsulinemia, hyperuricemia, hypertriglyceridemia, and hypertension. Tempol reduced blood glucose and insulin levels (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) in FT rats compared with their untreated counterparts. The vasoconstriction response to all agonists was lower in F rats than in control rats by about 35%-65% (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Vasoconstrictor responses to noradrenaline, phenylephrine, and methoxamine but not Ang II were about 41%-75% higher in FT rats compared with F rats (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Acute tempol infusion blunted responses to noradrenaline, methoxamine, and Ang II in control rats by 32%, 33%, and 62%, while it blunted responses to noradrenaline and Ang II in F rats by 26% and 32%, respectively (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), compared with their untreated counterparts. Superoxide radicals play a crucial role in controlling renal vascular responses to adrenergic agonists in insulin-resistant rats. Chronic but not acute tempol treatment enhances renal vascular responsiveness in fructose-fed rats.
Sheng li xue bao: [Acta physiologica Sinica]
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Papers by Mohammed H. Abdulla