TY - JOUR
T1 - 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
T2 - Correlation with topography of vascular endothelin-1 gene expression
AU - Li, Jin S.
AU - Deng, Li Y.
AU - Grove, Kevin
AU - Deschepper, Christian F.
AU - Schiffrin, Ernesto L.
PY - 1996/8
Y1 - 1996/8
N2 - 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.
AB - 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.
KW - aorta
KW - endothelium-derived factor
KW - nitric oxide
KW - receptors, endothelin
KW - resistance vessels
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U2 - 10.1161/01.HYP.28.2.188
DO - 10.1161/01.HYP.28.2.188
M3 - Article
C2 - 8707380
AN - SCOPUS:0029767930
SN - 0194-911X
VL - 28
SP - 188
EP - 195
JO - Hypertension
JF - Hypertension
IS - 2
ER -