A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril.
To evaluate the role of bradykinin in the antihypertrophic effect of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, we investigated the influence of HOE 140, a specific B2-receptor antagonist, on the effects of ramipril on left ventricular hypertrophy (LVH) in rats with aortic banding. Ramipril at a dose of 1 mg kg-1 day-1 for 6 weeks prevented the increase in blood pressure and development of LVH after aortic banding; plasma ACE activity was significantly inhibited. A lower dose of ramipril (10 micrograms kg-1 day-1 for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity, but prevented LVH after aortic banding. The antihypertrophic effects of the higher and the lower dose ramipril, as well as the antihypertensive action of the higher dose of ramipril were abolished by the coadministration of HOE 140 (500 micrograms kg-1 day-1). The present data show for the first time that the beneficial effects of an ACE-inhibitor on LVH in rats with hypertension caused by aortic banding can be prevented by a specific B2-receptor antagonist.
Linz
W
W
Department of Pharmacology, Hoechst AG, Frankfurt/Main, Germany.
Schölkens
B A
BA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000031:analogs & derivatives; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D009842:Oligopeptides; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin