Superoxide and its interaction with nitric oxide modulates renal function in prehypertensive Ren-2 transgenic rats.

Abstract:

OBJECTIVE:The present study was performed to examine the role of superoxide (O2*) and its interaction with nitric oxide (NO) in the regulation of renal function in prehypertensive heterozygous Ren-2 transgenic rats (TGR). METHODS:Renal responses to the O2* scavenger, tempol (150 microg/min per 100 g), and/or the NO synthase inhibitor, nitro-L-arginine methylester (L-NAME; 5 microg/min per 100 g), infused alone or in combination directly into the renal artery were evaluated in anesthetized heterozygous male TGR and aged-matched Hanover Sprague-Dawley rats (HanSD). RESULTS:There were no differences in arterial pressure (122 +/- 3 versus 115 +/- 2 mmHg), renal plasma flow (RPF; 2.09 +/- 0.1 versus 2.07 +/- 0.1 ml/min per g), glomerular filtration rate (GFR; 0.73 +/- 0.1 versus 0.74 +/- 0.1 ml/min per g) or sodium excretion (0.63 +/- 0.13 versus 0.67 +/- 0.16 micromol/min per g) between TGR and HanSD. Tempol alone caused significant increases in RPF and GFR (10 +/- 4% and 12 +/- 2%, respectively) in TGR but not in HanSD. Tempol also caused greater sodium excretory responses in TGR compared to HanSD (112 +/- 16% versus 43 +/- 7%; P < 0.05). 8-Isoprostane excretion was significantly higher in TGR than in HanSD (10.2 +/- 0.8 versus 6.5 +/- 0.7 pg/min per g), which was attenuated by tempol. L-NAME caused greater decreases in RPF and GFR in TGR (-34 +/- 4% and -22 +/- 4%, respectively) than in HanSD (-19 +/- 3% and -10 +/- 4%, respectively). Co-infusion of tempol partially attenuated the renal hemodynamic and excretory responses to L-NAME in TGR. CONCLUSIONS:These data suggest that the enhanced O2* activity and its interaction with NO during the prehypertensive phase in TGR modulates renal hemodynamic and excretory function, which may contribute to the development of hypertension in this transgenic rat model.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Kopkan L,Husková Z,Vanourková Z,Thumová M,Skaroupková P,Cervenka L,Majid DS

doi

10.1097/HJH.0b013e3282efb195

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

2257-65

issue

11

eissn

0263-6352

issn

1473-5598

pii

00004872-200711000-00013

journal_volume

25

pub_type

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