Comparison of effect of endothelin antagonism and angiotensin- converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N(ω)-nitro-L-arginine methyl ester: Correlation with topography of vascular endothelin-1 gene expression

Jin S. Li, Li Y. Deng, Kevin Grove, Christian F. Deschepper, Ernesto L. Schiffrin

    Research output: Contribution to journalArticle

    35 Scopus citations

    Abstract

    Inhibition of nitric oxide synthase by L-arginine analogues such as N(ω)-nitro-L-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHR) is associated with malignant hypertension and enhanced expression of the endothelin-1 gene in some blood vessels. In this study, SHR treated chronically with L-NAME (SHR-L-NAME) were given the angiotensin 1-converting enzyme inhibitor cilazapril or the endothelin-A/endothelin-B receptor antagonist bosentan for 3 weeks. Systolic pressure was lowered slightly by cilazapril (213±2 versus 229±2 mm Hg in untreated SHR-L-NAME, P<.01) but was not significantly lowered by bosentan (223±2 mm Hg). Hypertrophy of aorta and small arteries (coronary, renal, mesenteric, and femoral) was decreased by cilazapril treatment and unaffected by bosentan. Expression of the endothelin-1 gene was evaluated in SHR-L-NAME by in situ hybridization histochemistry, which showed that endothelin-1 expression was enhanced in the endothelium of aorta but not in small mesenteric arteries in these rats. The absence of enhancement of endothelin-1 gene expression in small arteries may account for the absence of increased severity of hypertrophy of small vessels in SHR-L-NAME and may be a mechanism whereby L-NAME inhibits cardiovascular growth. These results suggest that in the absence of enhanced small-artery endothelin-1 expression, endothelin antagonism does not lower blood pressure. The blood pressure lowering effect of angiotensin I- converting enzyme inhibition suggests a role for the reninangiotensin system in the malignant form of hypertension that develops in SHR treated with L- NAME.

    Original languageEnglish (US)
    Pages (from-to)188-195
    Number of pages8
    JournalHypertension
    Volume28
    Issue number2
    DOIs
    StatePublished - Aug 1996

    Keywords

    • aorta
    • endothelium-derived factor
    • nitric oxide
    • receptors, endothelin
    • resistance vessels

    ASJC Scopus subject areas

    • Internal Medicine

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