Increased nitric oxide activity in early renovascular
hypertension.
Dubey, Raghvendra K., Matthew A. Boegehold[tilde]n, Delbert G.
Gillespie, and Marinella Rosselli.
Department of Medicine, Center for Clinical Pharmacology,
University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582;
Department of Physiology, West Virginia University, Morgantown,
WV[tilde]n; and Department of Obstetrics and Gynecology, Clinic of
Endocrinology, University Hospital, Zurich, Switzerland
APStracts 2:0231R, 1995.
A decreased influence of nitric oxide (NO) in the peripheral
vasculature is associated with the pathophysiology of established
hypertension, and some studies suggest that increased blood pressure
positively correlates with decreased NO production. If so then the
increased arterial pressure in 1-kidney 1-clip (1K1C) hypertensive
rats should be associated with decreased circulating levels of
nitrite/nitrate (NO2/NO3; stable metabolites of NO) and cyclic
guanosine monophosphate (cGMP; mediator of NO action). We measured
serum NO2/NO3 and cGMP levels in early hypertensive 1K1C (2 weeks
after clipping) and sham-operated 1K normotensive rats, treated
orally with or without the NO-synthase inhibitor NG-nitro - L
-arginine methyl ester (L-NAME, 2 wk). Compared to 1K rats, NO2/NO3
and cGMP levels were increased in 1K1C hypertensive rats, but not in
1K1C rats treated with L-NAME. NO2/NO3 and cGMP levels in L-NAME
treated 1K and 1K1C rats were similar. Compared to 1K rats, systolic
blood pressure (SBP) was increased in 1K1C rats and in L-NAME treated
1K and 1K1C rats. The SBP increase in L-NAME treated 1K1C rats was
more rapid than in untreated 1K1C rats. In early hypertension,
increases in SBP positively correlated with increases in serum
NO2/NO3 and cGMP. After 2 weeks of hypertension, circulating NO2/NO3
levels gradually declined and reached pre-hypertension levels by the
5th week of hypertension. These results provide evidence for
increased NO synthesis in early hypertensive 1K1C rats, and this
increased NO could be a compensatory mechanism to slow the
development of hypertension in these animals.
Received 15 February 1995; accepted in final form 26 July 1995.
APS Manuscript Number R119-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.