N. Hutrikahonen et al., ARTERIAL RESPONSES TO BRADYKININ AFTER RAMIPRIL THERAPY IN EXPERIMENTAL-HYPERTENSION, Pharmacology & toxicology, 81(4), 1997, pp. 190-196
Angiotensin-converting enzyme inhibitors have been shown to potentiate
relaxations to kinins in several arteries, but the effects of long-te
rm therapy on the responses to bradykinin in normotensive and hyperten
sive animals remain largely unknown. Therefore, the effects of 12-week
-long ramipril therapy (1 mg kg(-1) day(-1)) on responses of mesenteri
c arterial rings in vitro were studied in spontaneously hypertensive r
ats and normotensive Wistar-Kyoto rats. Endothelium-dependent relaxati
ons of noradrenaline-precontracted rings to acetylcholine were similar
in normotensive rats and ramipril-treated hypertensive rats and more
pronounced than in untreated hypertensive group. Higher concentrations
of bradykinin (0.1-1 mu M) induced slight contractions in noradrenali
ne-precontracted endothelium-intact rings of normotensive groups and u
ntreated hypertensive group, whereas no response or a transient relaxa
tion were observed in ramipril-treated hypertensive rats. Interestingl
y in ramipril-treated hypertensive rats but not in the other groups, 2
0-min. pretreatment of arterial rings with ramiprilat unmasked or pote
ntiated the relaxations to bradykinin, and these bradykinin-induced re
laxations were effectively inhibited by the B-2-kinin receptor antagon
ist Hoe-140. In conclusion, ramipril treatment clearly improved endoth
elium-dependent arterial relaxation to acetylcholine, and potentiated
of even unmasked the dilatory response mediated via the endothelial B-
2-kinin receptor in spontaneously hypertensive rats. Since these enhan
cing effects on arterial relaxation in vitro could not be attributed t
o reduced breakdown of bradykinin, the present results suggest that lo
ng-term angiotensin-converting enzyme inhibition potentiated the actio
ns of kinins at level of B-2-kinin receptors.