Hypertension, Vol 19, 138-145, Copyright © 1992 by American Heart Association
V Cachofeiro, T Sakakibara and A Nasjletti
We investigated the role of kinins in the acute depressor effect of
captopril and ramiprilat in spontaneously hypertensive rats. Since the
vasodepressor action of kinins may be linked to the generation of
prostaglandins and endothelium-derived relaxing factors, we also
investigated the role of prostaglandins and nitric oxide in the blood
pressure reduction caused by angiotensin converting enzyme inhibitors. To
this end, we contrasted the hypotensive effects of captopril (10 mg/kg
i.v.), ramiprilat (2 mg/kg i.v.), and the angiotensin II antagonist DuP 753
(30 mg/kg i.v.) in spontaneously hypertensive rats with and without
pretreatment with a kinin antagonist (D-Arg-Arg-Pro-
Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid) (200 micrograms/kg/min
i.v.), an inhibitor of nitric oxide synthesis (NG- monomethyl-L-arginine)
(15 mg/kg + 10 mg/kg/hr i.v.), or an inhibitor of prostaglandin synthesis
(indomethacin) (10 mg/kg i.v.). The kinin antagonist did not affect blood
pressure in spontaneously hypertensive rats but did attenuate the
hypotensive effect of captopril and ramiprilat; the kinin antagonist did
not minimize the depressor action of DuP 753. The nitric oxide synthesis
inhibitor increased blood pressure in spontaneously hypertensive rats and
attenuated the hypotensive effect of captopril, ramiprilat, and DuP 753,
but it did not impede the hypotensive effect of sodium nitroprusside.
Pretreatment of hypertensive rats with indomethacin did not modify the
acute hypotensive effect of ramiprilat or captopril. These data suggest a
contribution of endogenous kinins and nitric oxide to the acute
antihypertensive effect of captopril and ramiprilat in spontaneously
hypertensive rats and of nitric oxide to the hypotensive effect of DuP 753.
ARTICLES
Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension
Department of Pharmacology, New York Medical College, Valhalla 10595.
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