Hypertension, Vol 23, 476-484, Copyright © 1994 by American Heart Association
A Papapetropoulos, N Marczin, MD Snead, C Cheng, A Milici and JD Catravas
Endothelium-derived relaxing factor and exogenous nitrovasodilators are
thought to produce smooth muscle relaxation by activation of soluble
guanylate cyclase. To investigate whether diminished cyclic GMP (cGMP)
accumulation underlies the differences in vascular reactivity to
nitrovasodilators between Wistar-Kyoto (WKY) rats and spontaneously
hypertensive rats (SHR), we determined cGMP formation in aortic smooth
muscle cells from the two strains. Both cultured cells and aortic rings
from 12- to 14-week-old SHR accumulated greater amounts of cGMP on
stimulation with exogenous nitrovasodilators (ie, sodium nitroprusside)
than those from WKY rats, whereas there was no difference observed in cells
from prehypertensive animals (5- to 6-week old) between the two strains.
Responsiveness of smooth muscle cells to endothelium-derived relaxing
factor was investigated in cocultures of bovine aortic endothelial cells
(BAE) and smooth muscle cells from SHR and WKY rats. cGMP accumulation
elicited by endothelium-derived relaxing factor released either basally or
in response to bradykinin and the calcium ionophore A23187 was greater in
smooth muscle from 12- to 14-week-old SHR than from age-matched WKY rats
(80 +/- 17 versus 11 +/- 2 for basal; 152 +/- 12 versus 80 +/- 26 for
A23187; 163 +/- 21 versus 40 +/- 12 pmol/mg protein per 15 minutes for
bradykinin) in SHR/BAE and WKY/BAE cocultures, respectively. Northern blot
analysis of steady- state messenger RNA levels for the beta 1 subunit of
soluble guanylate cyclase revealed higher levels of the message in
SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Smooth muscle cell responsiveness to nitrovasodilators in hypertensive and normotensive rats
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
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