[show abstract][hide abstract] ABSTRACT: 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.
Yakugaku zasshi journal of the Pharmaceutical Society of Japan 03/2011; 131(3):431-6. · 0.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats.
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).
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.
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.
Upsala journal of medical sciences 11/2010; 116(1):18-25. · 0.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Regulation of renal function and haemodynamics are under a direct control from the renal sympathetic nerves and renal denervation produces overt diuresis and natriuresis in several mammalian species. However, the inter-related series of changes in renal function and haemodynamics following acute renal denervation (ARD) is not fully understood. Thus, we aimed to investigate and relate the changes in renal function and haemodynamics following acute unilateral renal denervation in anaesthetized Sprague Dawley (SD) rats.
Male SD rats were fasted overnight, anaesthetized with sodium pentobarbitone (60 mg/kg ip), denervated by application of phenol to the left renal artery and maintained on an intravenous (iv) infusion of isotonic saline for 2 h. Throughout this period, six urine and plasma samples were taken at 20-min intervals to study kidney function parameters. In a different set of experiments, renal nerve stimulation (RNS) was carried out to characterize the changes in renal vasoconstrictor responses following ARD.
Denervated animals showed significantly (P<0.05 vs. control innervated rats) higher urine flow rate (UFR), absolute sodium excretion (UNaV), fractional sodium excretion (FENa) and glomerular filtration rate (GFR). The renal vasoconstrictor responses to RNS were significantly (P<0.05) lower in denervated rats as compared to the innervated counterparts. However, no appreciable differences were seen in the mean arterial pressure (MAP), plasma sodium (PNa), basal renal blood flow (RBF) and basal renal vascular resistance (RVR) in both innervated and denervated SD rats.
Natriuresis, diuresis, enhanced GFR and impaired vasoconstriction in response to RNS are typical and instant responses to ARD in SD rats. Renal sympathetic nerves serve more important role in salt and water conservation than in dynamic autoregulation of RBF under normal sympathetic tone; yet, their effects on renal haemodynamics become more evident in the presence of augmented renal sympathetic nerve activity (RSNA).
The Indian journal of medical research 01/2010; 131:76-82. · 2.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background. Elevated dietary sodium intake exacerbates the elevation of blood pressure in spontaneously hypertensive
rats (SHR) which is associated with increased renal vascular resistance and fluid reabsorption. The renal
sympathetic nerves exert their action via α1-adrenoceptors (α1-AR) with α1A as the major subtype in regulating renal
hemodynamics and excretory function.
Objectives. This study investigated whether the contribution of α1A-AR in regulating renal vasoconstriction and
excretory function was enhanced in SHR receiving high sodium intake.
Material and Methods. SHR received either water (SHRNNa) or normal saline (SHRHNa) for six weeks. Metabolic
cage studies followed by acute experiments were carried out on these SHR to examine renal vasoconstrictor and
excretory responses to catecholamine viz. noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in the
presence and absence of a α1A-AR blocker, 5-methylurapidil (5-MeU).
Results. Daily water intake and urine output were increased in SHRHNa (P < 0.05 vs. SHRNNa). Renal cortical vascular
responses to NA, PE and ME were enhanced in SHRHNa (P < 0.05 vs. SHRNNa) and the greatest effect was
seen with ME. Intra-renal infusion of PE caused antidiuresis and antinatriuresis. Irrespective of the sodium intake,
5-MeU markedly blunted adrenergically induced renal cortical vasoconstrictions in SHR, while the antinatriuretic and antidiuretic responses to PE were inhibited by 5-MeU in SHRHNA only (P < 0.05). Conclusions. The data suggest that, irrespective of the level of dietary sodium intake, α1A-ARs are the functional subtypes in SHR. However, there also appears to be a role for α1A-AR in mediating enhanced renal cortical vascular resistance, augmented tubular Na+ and water reabsorption in SHRHNa rats (Adv Clin Exp Med 2011, 20, 1, 47–55).
Advances in Clinical and Experimental Medicine 01/2010; 20:47–55. · 0.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition.
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).
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.
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.
Kidney and Blood Pressure Research 10/2009; 32(5):349-59. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background. It is well known that the pathogenesis of most renal diseases is associated with alterations in renal hemodynamics and also that the regulation of renal hemodynamics is under the direct control of renal sympathetic nerve activity. Objectives. The role of the renal sympathetic nervous system in the early deterioration of renal hemodynamics in rats with pathophysiological states of renal impairment was investigated. Material and Methods. Male Sprague Dawley rats were induced with acute renal failure or diabetes mellitus by cisplatin or streptozotocin (STZ), respectively. Cisplatin−induced renal failure was confirmed by impaired renal function and the diabetic state and early renal impairment were confirmed by hyperglycemia, changes in physio− logical parameters, and renal function. The hemodynamic study was conducted on anesthetized rats 7 days after cisplatin or STZ administration. During the acute study the renal sympathetic nerves were electrically stimulated at increasing frequencies and the responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Results. In the innervated rats with renal impairment, renal nerve stimulation (RNS) caused significant attenuation (all P < 0.05 vs. innervated control) of the renal vasoconstrictor responses. These responses were markedly (all P < 0.05) abolished when renal denervation was performed; however, they appeared significantly (all P < 0.05) higher than the denervated control counterparts. Conclusions. The findings strongly suggest an early involvement of renal sympathetic nerve action in the patho− genesis of renal impairment accompanying renal failure and diabetes. The data further suggest an early enhance− ment of renal sensitivity to intrarenal norepinephrine upon the removal of renal sympathetic tone by denervation (Adv Clin Exp Med 2009, 18, 3, 205-214).