Role of nNOS in Regulation of Renal Function in Hypertensive Ren-2 Transgenic Rats
 

L. ČERVENKA^1,5, H.J. KRAMER², J. MALݹ, I. VANĚČKOVÁ^1,5, A. BÄCKER²,
D. BOKEMEYER², M. BADER³, D. GANTEN³, K.D. MITCHELL⁴

¹Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²Section of Nephrology, Medical Policlinic, Department of Medicine, University of Bonn, Bonn, ³Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany, ⁴Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, USA and ⁵Center for Experimental Cardiovascular Research, Prague, Czech Republic

Received April 8, 2002
Accepted July 30, 2002
 

Summary
The present study was performed to evaluate the role of neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) during the developmental phase of hypertension in transgenic rats harboring the mouse Ren-2 renin gene (TGR). The first aim of the present study was to examine nNOS mRNA expression in the renal cortex and to assess the renal functional responses to intrarenal nNOS inhibition by S-methyl-L-thiocitrulline (L-SMTC) in heterozygous TGR and in age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). The second aim was to evaluate the role of the renal sympathetic nerves in mediating the renal functional responses to intrarenal nNOS inhibition. Thus, we also evaluated the effects of intrarenal L-SMTC administration in acutely denervated TGR and HanSD. Expression of nNOS mRNA in the renal cortex was significantly increased in TGR compared with HanSD. Intrarenal administration of L-SMTC decreased the glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion and increased renal vascular resistance (RVR) in HanSD. In contrast, intrarenal inhibition of nNOS by L-SMTC did not alter GFR, RPF or RVR and elicited a marked increase in sodium excretion in TGR. This effect of intrarenal L-SMTC was not observed in acutely denervated TGR. These results suggest that during the developmental phase of hypertension TGR exhibit an impaired renal vascular responsiveness to nNOS derived NO or an impaired ability to release NO by nNOS despite enhanced expression of nNOS mRNA in the renal cortex. In addition, the data indicate that nNOS-derived NO increases tubular sodium reabsorption in TGR and that the renal nerves play an important modulatory role in this process.

Key words
Hypertension · Transgenic rat · Neuronal nitric oxide synthase · Renal nerves · Renal hemodynamics

Reprint requests
L. Červenka, M.D., Ph.D., Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, CZ-140 00 Prague 4, Czech Republic. Fax: +4202 41721666. E-mail: luce@medicon.cz

ISSN 0862 - 8408