Hypertension, Vol 22, 569-576, Copyright © 1993 by American Heart Association
GA Gray, M Clozel, JP Clozel and HR Baumgartner
Hypertension is associated with an intimal dysfunction characterized by
endothelium-dependent constriction to serotonin, decreased endothelium-
dependent relaxation to acetylcholine, and a subendothelial infiltration of
monocyte-macrophages. The goal of our study was to evaluate the effect of
long-term calcium channel blockade with Ro 40- 5967, a new long-acting
calcium channel blocker, on these alterations in aortas of spontaneously
hypertensive rats (SHR). Arterial blood pressure was decreased by Ro
40-5967. In aortas from Ro 40-5967-treated SHR, the serotonin ratio
(maximal contraction to serotonin on rings with endothelium over maximal
contraction on paired rings without endothelium) was reduced (1.14 +/-
0.10) compared with control SHR (1.72 +/- 0.12, P < .01) because of
inhibition of maximal contraction in rings with endothelium. This effect of
Ro 40-5967 was partially reversed by an inhibitor of nitric oxide (NO)
synthase, NG-nitro-L- arginine-methyl ester, and partially inhibited in the
presence of the thromboxane/prostaglandin H2 receptor antagonist AH 23848.
Maximal relaxation to acetylcholine in rings with endothelium was increased
by Ro 40-5967. In rings without endothelium, Ro 40-5967 treatment enhanced
the sensitivity to sodium nitroprusside-induced relaxation. Cyclic GMP
content, an indicator of NO release, was not increased in aortas from Ro
40-5967-treated SHR. Thus, improvement of endothelial function was probably
achieved by facilitating the action of NO at the level of the smooth muscle
cells and by reducing prostaglandin H2-induced constriction. Finally, the
number of monocyte-macrophages in the subendothelium was decreased by Ro
40-5967. 40-5967.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Effects of calcium channel blockade on the aortic intima in spontaneously hypertensive rats
Preclinical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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