M. Kahonen et al., Losartan and enalapril therapies enhance vasodilatation in the mesenteric artery of spontaneously hypertensive rats, EUR J PHARM, 368(2-3), 1999, pp. 213-222
We studied the effects of 10-week long enalapril and losartan treatments (4
and 15 mg kg(-1) day(-1), respectively) on mesenteric arterial function in
vitro in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)
. The relaxations of noradrenaline-precontracted rings to acetylcholine, ni
troprusside and cromakalim were similar in WKY and enalapril- and losartan-
treated SHR, and more pronounced than in untreated SHR. The responses to ac
etylcholine were attenuated by N-G-nitro-L-arginine methyl ester in WKY and
drug-treated SHR, but were completely inhibited in untreated SHR. When hyp
erpolarization of smooth muscle was prevented by KCl-induced precontraction
s, no differences were found in the relaxations to acetylcholine and nitrop
russide between the groups, and the dilatations to cromakalim were abolishe
d. Moreover, in noradrenaline-precontracted rings of drug-treated SHR, the
addition of tetraethylammonium attenuated the nitric oxide synthase and cyc
looxygenase-resistant relaxations to acetylcholine and abolished the enhanc
ed dilatations to nitroprusside. In conclusion, since the enhancement of va
sorelaxation in enalapril- and losartan-treated SHR was abolished by condit
ions preventing hyperpolarization, the improved vasodilatation following th
ese therapies could be attributed to enhanced vasodilatation via K+ channel
s in this model of hypertension. (C) 1999 Elsevier Science B.V. All rights
reserved.