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

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 alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) 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 AT(1) and alpha(1)-adrenoceptor subtypes.

[1]  C. Long,et al.  Cross Talk Between Angiotensin AT1 and α1-Adrenergic Receptors : Angiotensin II Downregulates α1a-Adrenergic Receptor Subtype mRNA and Density in Neonatal Rat Cardiac Myocytes , 1997 .

[2]  R A Mueller,et al.  Effects of acute unilateral renal denervation in the rat. , 1975, The Journal of clinical investigation.

[3]  E. Johns,et al.  Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype causing vasoconstriction in the kidney of the rat. , 2007, European journal of pharmacology.

[4]  G. Feuerstein,et al.  The Effect of Diet on Simvastatin and Losartan Enhancement of Endothelial Function , 2007, Clinical and experimental hypertension.

[5]  M. Perazella,et al.  Renin-angiotensin-aldosterone system: Fundamental aspects and clinical implications in renal and cardiovascular disorders , 2003, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[6]  G. Feuerstein,et al.  Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension. , 2005, American journal of hypertension.

[7]  R. Kontermann.  Recombinant bispecific antibodies for cancer therapy , 2005, Acta Pharmacologica Sinica.

[8]  R. Blantz,et al.  Changes in glomerular hemodynamic response to angiotensin II after subacute renal denervation in rats. , 1986, The Journal of clinical investigation.

[9]  E. Johns,et al.  Cisplatin-induced nephrotoxicity causes altered renal hemodynamics in Wistar Kyoto and spontaneously hypertensive rats: role of augmented renal alpha-adrenergic responsiveness. , 2007, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[10]  G. Dibona.  Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function. , 2000, Hypertension.

[11]  S. Malpas,et al.  Role of Angiotensin II in the Neural Control of Renal Function , 2003, Hypertension.

[12]  G. Dibona,et al.  Neural control of renal function. , 1997, Physiological reviews.

[13]  G. Grassi.  Renin-angiotensin-sympathetic crosstalks in hypertension: reappraising the relevance of peripheral interactions. , 2001, Journal of hypertension.

[14]  K. Berecek,et al.  Effects of angiotensin inhibition and renal denervation in two-kidney, one clip hypertensive rats. , 1986, Hypertension.

[15]  S. Malpas,et al.  Is the chronically denervated kidney supersensitive to catecholamines? , 2002, American journal of physiology. Regulatory, integrative and comparative physiology.

[16]  J. Sadowski,et al.  Reinvestigation of denervation diuresis and natriuresis in conscious dogs. , 1979, Archives internationales de physiologie et de biochimie.

[17]  C. Johnston,et al.  Specific Increase in Renal αl-Adrenergic Receptors Following Unilateral Renal Denervation , 1985 .

[18]  C. Johnston,et al.  Specific increase in renal alpha 1-adrenergic receptors following unilateral renal denervation. , 1985, Journal of receptor research.

[19]  N. Abdullah,et al.  The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats , 2004, British journal of pharmacology.

[20]  E. Johns,et al.  α1-Adrenoceptor Subtypes Mediating Adrenergic Vasoconstriction in Kidney of Two Kidney, One‐Clip Goldblatt and Deoxycorticosterone Acetate‐Salt Hypertensive Rats , 1994 .

[21]  W. Arendshorst,et al.  α1-Adrenoceptor subtypes in rat renal resistance vessels : In vivo and in vitro studies , 2000 .

[22]  H. Ehmke,et al.  Maintenance of blood pressure in normotensive dogs by endothelin. , 1999, The American journal of physiology.

[23]  K. Minneman,et al.  Recent progress in α1-adrenergic receptor research , 2005, Acta Pharmacologica Sinica.

[24]  G. Dibona.  Renin-Angiotensin System in the Control of Renal Function Nervous Kidney : Interaction Between Renal Sympathetic Nerves and the , 2000 .

[25]  E. Johns,et al.  Nitric Oxide Modulation of Neurally Induced Proximal Tubular Fluid Reabsorption in the Rat , 2002, Hypertension.

[26]  E. Johns,et al.  Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow , 2001, The Journal of physiology.

[27]  E. Johns,et al.  Alpha 1-adrenoceptor subtypes mediating adrenergic vasoconstriction in kidney, one-clip Goldblatt and deoxycorticosterone acetate-salt hypertensive rats. , 1994, Journal of cardiovascular pharmacology.

[28]  G. Dibona,et al.  Renal nerves in compensatory renal response to contralateral renal denervation. , 1980, The American journal of physiology.

[29]  M. Crespo.  Interaction between AT1 and alpha1-adrenergic receptors in cardiomyopathic hamsters. , 2000, Journal of cardiac failure.