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The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H2S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in spontaneously hypertensive rats (SHR) that were diabetic. Eighteen SHR were divided into three groups: SHR, SHR diabetic, and SHR diabetic treated with a group of Wistar-Kyoto rats serving as normotensive nondiabetic control. Diabetes was induced with streptozotocin (STZ) in two groups and one diabetic group received sodium hydrosulfide (NaHS), a H2S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H2S levels, creatinine concentrations, and electrolytes were measured on three different occasions throughout the 35-day period. Diabetic SHR had higher blood pressure, lower plasma and urinary H2S levels, and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance, and decreased urinary sodium-to-potassium ratio and renal cortical blood perfusion. NaHS reduced blood pressure, increased H2S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H2S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.

Background: This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats., Methods: Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME)., Results: In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists., Conclusions: Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats.

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.

Background: 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., Methods: Male Sprague Dawley (SD) rats (each group, n=6) were fasted overnight, anesthetized with pentobarbital sodium (60 mg/kg intraperitoneal), denervated by application of phenol to the left renal artery and maintained on an intravenous infusion of saline for 2 hours. During this period, 6 urine and plasma samples were collected at 20-minute intervals to study kidney function parameters., Results: In denervated rats, there were significantly higher (all p<0.05 vs. innervated control) urine flow rate (UFR), glomerular filtration rate (GFR), absolute sodium excretion (U(Na)V), fractional sodium excretion (FE(N)a), absolute potassium excretion (U(K)V), fractional potassium excretion (FE(K)) and urinary sodium to urinary potassium ratio (U(Na)/U(K)). No appreciable differences were seen in the mean arterial pressure (MAP) and plasma sodium (P(Na)) between denervated and innervated SD rats. However, plasma potassium (P(K)) levels were significantly lower (p<0.05) in denervated rats as compared with innervated counterparts., Conclusions: There is a possible involvement of renal nerves in the regulation of renal potassium handling. This effect is largely attributable to a direct action of renal sympathetic nerves on the renal tubular segments.

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.

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.

Aim: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition., Methods: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na(+) (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (alpha-adrenoceptor agonist), phenylephrine (alpha(1)-adrenoceptor agonist) and methoxamine (alpha(1A)-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca(2+) channel blocker), 5-methylurapidil (alpha(1A)-adrenoceptor antagonist), chloroethylclonidine (alpha(1B)-adrenoceptor antagonist) and BMY 7378 (alpha(1D)-adrenoceptor antagonist)., Results: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses., Conclusion: The data demonstrated that there was a functional coexistence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic alpha-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR., (Copyright 2009 S. Karger AG, Basel.)

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.