Hypertension, Vol 24, 322-328, Copyright © 1994 by American Heart Association
N Bank, HS Aynedjian and GA Khan
Either acute or chronic inhibition of nitric oxide synthesis by L- arginine
analogues results in increases in mean arterial pressure and reductions in
renal blood flow. The role of endogenous vasoconstrictors in mediating
these effects is not entirely clear. In the present study, nitric oxide was
inhibited in male Sprague-Dawley rats by oral administration of
nitro-L-arginine for 3 weeks. At the end of this time, mean arterial
pressure was 30 to 40 mm Hg higher than in normal controls, renal blood
flow and glomerular filtration rate were 25% to 30% lower, and renal
vascular resistance was markedly increased. Intravenous infusion of
receptor antagonists for angiotensin II, thromboxane, epinephrine, and
endothelin-1 had no significant effect on the hypertension. Inhibition of
prostaglandin synthesis and furosemide- induced diuresis in the presence of
angiotensin blockade also had no effect on blood pressure. Renal vascular
resistance was also unaffected by these interventions, except that
saralasin did reduce renal resistance in both control and nitric
oxide-inhibited groups. However, the absolute level of renal vascular
resistance remained higher in the latter group. Calcium channel blockade
partially corrected blood pressure and renal resistance, but the levels
remained significantly higher than in control animals. The findings are
consistent with the view that the increase in vascular smooth muscle tone
caused by inhibition of nitric oxide synthesis cannot be accounted for by
overexpression of common endogenous vasoconstrictors. Rather, the
generalized increase in vascular smooth muscle tone appears to be due to a
direct effect of reduced nitric oxide availability, which may lead to an
increase in intracellular calcium concentration or sensitivity.
ARTICLES
Mechanism of vasoconstriction induced by chronic inhibition of nitric oxide in rats
Department of Medicine, Montefiore Medical Center, Bronx, NY 10467.
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