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Effect of acute unilateral renal denervation on renal hemodynamics in spontaneously hypertensive rats

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Abstract:

Summary

1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation.

2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg−1 i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II.

3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats.

4 The data obtained in denervated rats suggested an enhanced sensitivity of the α1-adrenoceptors to adrenergic agonists and possible increase of AT1 receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT1 and α1-adrenoceptor subtypes.

Keywords: losartan; renal hemodynamics; spontaneously hypertensive rat; α1-adrenoceptors

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1474-8673.2008.00421.x

Affiliations: 1: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia 2: Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia 3: Department of Physiology, Aras Windle, University College Cork, College Road, Cork, Ireland

Publication date: April 1, 2008

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