Roles of nitric oxide and oxidative stress in the regulation of blood pressure and renal function in prehypertensive Ren-2 transgenic rats

Item Type:	Article
Title:	Roles of nitric oxide and oxidative stress in the regulation of blood pressure and renal function in prehypertensive Ren-2 transgenic rats
Creators Name:	Vaneckova, I. and Kramer, H.J. and Novotna, J. and Kazdova, L. and Opocensky, M. and Bader, M. and Ganten, D. and Cervenka, L.
Abstract:	Aims: The present study was performed to evaluate the role of nitric oxide (NO) and its interaction with superoxide anion (O2-) in the regulation of blood pressure (BP) and renal function during the developmental phase of hypertension in Ren-2 transgenic rats (TGR). The first aim was to compare BP and renal functional responses to acute NO synthase (NOS) inhibition achieved by intravenous (i.v.) infusion of Nω-nitro-L-arginine- methyl ester (L-NAME) in prehypertensive heterozygous TGR and in transgene-negative Hannover Sprague-Dawley (HanSD) rats. The second aim was to evaluate whether scavenging of O2- by infusion of the superoxide dismutase mimetic tempol increases NO bioavailability which therefore should augment BP and renal functional responses to L-NAME. Methods: Rats were anesthetized, prepared for clearance experiments and BP and renal functional responses were evaluated in response to i.v. L-NAME administration (20 μg·100 g-1·min-1) without or with tempol pretreatment (i.v., 300 μg·100 g-1·min -1). In renal cortical tissue, nitrotyrosine protein expression was assessed by immunoblotting as marker of O2- production and urinary 8-epi-PGF2α excretion as marker of intrarenal oxidative stress was assessed by enzyme immunoassay. Results: BP, glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion were similar in TGR and HanSD. L-NAME infusion induced greater increases in BP in TGR than in HanSD (+42 ± 4 vs. +25 ± 3 mm Hg, p < 0.05). In the absence of a significant change in GFR, L-NAME caused similar decreases in RPF (-32 ± 6 and -25 ± 4%, p < 0.05) in TGR and HanSD. Despite significantly higher renocortical expression of nitrotyrosine and urinary 8-epi-PGF2α excretion in TGR than in HanSD, pretreatment with tempol did not augment the rise in BP and the decrease in RPF induced by L-NAME. Conclusions: The greater BP response to L-NAME in TGR suggests that prehypertensive TGR exhibit an enhanced NO activity in the systemic vasculature as compared with HanSD. Despite increased intrarenal oxidative stress in TGR, the dependency of the intrarenal vascular tone on NO appears to be similar in TGR and HanSD. The lack of a compensatory increase in renal NO activity may partially account for the enhanced renal vascular response to ANG II present in TGR. Copyright
Keywords:	Glomerular filtration rate, Hypertension, Nitric oxide synthase, Renal plasma flow, Sodium excretion, Tempol, Animals, Mice
Source:	Kidney and Blood Pressure Research
ISSN:	1420-4096
Publisher:	Karger
Volume:	28
Number:	2
Page Range:	117-126
Date:	1 January 2005
Official Publication:	https://doi.org/10.1159/000084649
PubMed:	View item in PubMed

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