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

Citation
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
Citations number
42
Categorie Soggetti
Peripheal Vascular Diseas",Hematology
Journal title
ISSN journal
00097322
Volume
95
Issue
1
Year of publication
1997
Pages
240 - 244
Database
ISI
SICI code
0009-7322(1997)95:1<240:VEGAEO>2.0.ZU;2-T
Abstract
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.