Document Detail

Role of nNOS in regulation of renal function in angiotensin II-induced hypertension.
MedLine Citation:
PMID:  11509490     Owner:  NLM     Status:  MEDLINE    
Previous studies have indicated that in normotensive rats, NO produced by neuronal NO synthase (nNOS) plays an important role in modulating tubuloglomerular feedback (TGF)-mediated afferent arteriolar constriction. It has also been shown that in angiotensin (Ang) II-infused hypertensive rats, there is a reduced ability of nNOS-derived NO to counteract this vasoconstriction. The present study was performed to (1) assess in vivo renal functional responses to intrarenal nNOS inhibition in control and Ang II-infused rats and (2) determine whether changes in renal function following nNOS inhibition are mediated by unopposed stimulation of Ang II receptor subtype 1 (AT(1)). Wistar rats were infused with either saline (SAL) or Ang II (80 ng/min) by osmotic minipumps implanted subcutaneously. Mean arterial blood pressure of SAL- and Ang II-infused rats on day 13 after implantation averaged 121+/-4 (n=28) and 151+/-5 (n=30), respectively (P<0.05). There were no differences in glomerular filtration rate (GFR) (0.68+/-0.09 versus 0.59+/-0.09 mL. min(-1). g(-1)), renal plasma flow (RPF) (2.66+/-0.31 versus 2.34+/-0.39 mL. min(-1). g(-1)), and absolute sodium excretion (0.37+/-0.07 versus 0.42+/-0.09 micromol. min(-1). g(-1)). Intrarenal infusion of SAL did not change GFR, RPF, and sodium excretion in either SAL-infused (n=7) or Ang II-infused rats (n=8). Acute intrarenal administration of the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.3 mg/h) decreased GFR, RPF, and sodium excretion in SAL-infused rats (n=9) by 29+/-4%, 38+/-4%, and 70+/-4% compared with control values (P<0.05). The pretreatment by the AT(1) receptor antagonist candesartan (750 ng IR) in SAL-infused rats (n=7) effectively prevented the decrease in RPF (-3+/-3%) elicited by nNOS inhibition and resulted in an increase in GFR (+25+/-12, P<0.05) and a concomitant greater increase in sodium excretion (84+/-12%, P<0.05) compared with control values. In contrast, in Ang II-infused rats (n=10) intrarenal inhibition of nNOS by L-SMTC did not cause significant decreases in GFR, RPF and sodium excretion (-2+/-2%, -15+/-10%, and -14+/-10%, respectively). These results suggest that in normotensive rats nNOS-derived NO counteracts Ang II-mediated vasoconstriction in the pre- and postglomerular microcirculation. Furthermore, Ang II-infused rats exhibit an impaired ability to release NO by nNOS. Decreased nNOS activity is likely to account at least partially for the enhanced TGF responsiveness in Ang II-infused rats and thus may contribute to the maintenance of hypertension in this model.
L Cervenka; H J Kramer; J Malý; J Heller
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  38     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-17     Completed Date:  2001-08-30     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  280-5     Citation Subset:  IM    
Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
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MeSH Terms
Angiotensin II
Angiotensin Receptor Antagonists
Benzimidazoles / pharmacology
Blood Pressure / drug effects
Citrulline / analogs & derivatives,  pharmacology
Enzyme Inhibitors / pharmacology
Glomerular Filtration Rate / drug effects
Hypertension, Renal / chemically induced,  enzymology*,  physiopathology*
Kidney / blood supply,  enzymology,  physiopathology
Natriuresis / drug effects
Nitric Oxide Synthase / antagonists & inhibitors,  physiology*
Nitric Oxide Synthase Type I
Rats, Wistar
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Renal Plasma Flow / drug effects
Tetrazoles / pharmacology
Thiourea / analogs & derivatives,  pharmacology
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Benzimidazoles; 0/Enzyme Inhibitors; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Tetrazoles; 11128-99-7/Angiotensin II; 156719-41-4/S-methylthiocitrulline; 372-75-8/Citrulline; 62-56-6/Thiourea; EC Oxide Synthase; EC Oxide Synthase Type I; EC protein, rat; S8Q36MD2XX/candesartan

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