VASCULAR ENDOTHELIN-1 GENE-EXPRESSION AND EFFECT ON BLOOD-PRESSURE OFCHRONIC ET(A) ENDOTHELIN RECEPTOR ANTAGONISM AFTER NITRIC-OXIDE SYNTHASE INHIBITION WITH L-NAME IN NORMAL RATS
P. Sventek et al., VASCULAR ENDOTHELIN-1 GENE-EXPRESSION AND EFFECT ON BLOOD-PRESSURE OFCHRONIC ET(A) ENDOTHELIN RECEPTOR ANTAGONISM AFTER NITRIC-OXIDE SYNTHASE INHIBITION WITH L-NAME IN NORMAL RATS, Circulation, 95(1), 1997, pp. 240-244
Background Vascular expression of the endothelin-1 gene may be associa
ted with severe vascular hypertrophy. Because in rats, inhibition of N
O synthase with the L-arginine analogue N-omega-nitro-L-arginine methy
l ester (L-NAME) induces blood pressure elevation associated with litt
le cardiovascular hypertrophy, we studied vascular endothelin-1 gene e
xpression in L-NAME-treated rats and the effects of chronic endothelin
antagonism. Methods and Results Sprague-Dawley rats received 100 mg .
kg(-1). d(-1) L-NAME in their drinking water for 3 weeks. Systolic bl
ood pressure rose to 189+/-3 mm Hg (P<.001 versus control rats). By No
rthern blot analysis, endothelin-1 mRNA levels were similar in aortas
and mesenteric arteries of control and L-NAME-treated rats. The blood
pressure of L-NAME hypertensive rats treated with the ET(A)-selective
endothelin receptor antagonist A-127722 for 3 weeks at a low dose (10
mg . kg(-1). d(-1)) and a high dose (30 mg . kg(-1). d(-1)) was not di
fferent from that of rats receiving L-NAME but nor the endothelin anta
gonist. Treatment with the ACE inhibitor cilazapril lowered the blood
pressure of L-NAME-treated rats equally whether or not they were recei
ving the ET(A) antagonist. Conclusions These results indicate that the
endothelin system does not participate to an important degree in the
mechanisms leading to elevated blood pressure after chronic NO synthas
e inhibition with L-NAME in normal rats. In the chronic model of L-NAM
E-induced hypertension, blockade of the renin-angiotensin system does
not unmask an endothelin-dependent vasopressor tone. In addition, eith
er NO does not regulate vascular endothelin-1 gene expression or L-NAM
E exerts an inhibitory effect on endothelin expression in blood vessel
s.