Vascular endothelin-1 gene expression and effect on blood pressure of chronic ETA endothelin receptor antagonism after nitric oxide synthase inhibition with L-NAME in normal rats.
BACKGROUND: Vascular expression of the endothelin-1 gene may be associated with severe vascular hypertrophy. Because in rats, inhibition of NO synthase with the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) induces blood pressure elevation associated with little cardiovascular hypertrophy, we studied vascular endothelin-1 gene expression 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 blood pressure rose to 189 +/- 3 mm Hg (P < .001 versus control rats). By Northern 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 ETA-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 different from that of rats receiving L-NAME but not the endothelin antagonist. Treatment with the ACE inhibitor cilazapril lowered the blood pressure of L-NAME-treated rats equally whether or not they were receiving the ETA 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 synthase inhibition with L-NAME in normal rats. In the chronic model of L-NAME-induced hypertension, blockade of the renin-angiotensin system does not unmask an endothelin-dependent vasopressor tone. In addition, either NO does not regulate vascular endothelin-1 gene expression or L-NAME exerts an inhibitory effect on endothelin expression in blood vessels.[1]References
- Vascular endothelin-1 gene expression and effect on blood pressure of chronic ETA endothelin receptor antagonism after nitric oxide synthase inhibition with L-NAME in normal rats. Sventek, P., Turgeon, A., Schiffrin, E.L. Circulation (1997) [Pubmed]
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