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(Hypertension. 1996;28:188-195.)
© 1996 American Heart Association, Inc.

Articles

Comparison of Effect of Endothelin Antagonism and Angiotensin-Converting Enzyme Inhibition on Blood Pressure and Vascular Structure in Spontaneously Hypertensive Rats Treated With N-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

the Medical Research Council Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal (Canada).

Inhibition of nitric oxide synthase by L-arginine analogues such as N-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 I–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 renin-angiotensin system in the malignant form of hypertension that develops in SHR treated with L-NAME.

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

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