Role of nNOS in Regulation of Renal Function in
Hypertensive Ren-2 Transgenic Rats
L. ČERVENKA1,5,
H.J. KRAMER2, J. MALÝ1,
I. VANĚČKOVÁ1,5, 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
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