[Inhibition of the enzyme of conversion and cardioprotection: role of bradykinins].
Ramipril, a converting enzyme inhibitor, was first studied in rats with aortic stenosis, an experimental model of reno-vascular hypertension. In this study, ramipril has an antihypertrophic cardiac effect, independently to its hypotensive effect. The co-administration of Hoe 140, a specific antagonist of bradykinin receptors blocked totally the effect of ramipril on blood pressure, cardiac hypertrophy and on concentration of cGMP. These effects can therefore be explained by an accumulation of bradykinins. Furthermore, we investigated the preventing effects of ramipril on left ventricular hypertrophy, on growth of cardiac capillaries using SHR rats, treated in utero and during the 20 weeks following birth with two doses: a relatively high dose (1 mg/kg/day) and a low dose (0.01 mg/kg/day). Animals treated with a low dose of ramipril presented a high blood pressure similar to that observed in the control group. At the end of the treatment, the converting enzyme activity was inhibited in both groups. An increase in the growth of cardiac capillaries and of the cardiac concentration of glycogen and a decrease in the cardiac concentration of citric acid was observed in both groups. The ventricular weight decreased only in the high dose treatment group. This results demonstrated that early treatment with converting enzyme inhibitor even with a low dose which was unable to prevent the development of hypertension and of left ventricular hypertrophy. We could therefore draw a hypothesis of an accumulation of bradykinin due to the converting enzyme inhibitor which could explain in part this effect through an improvement of cardiac metabolism.
Unger
T
T
Institut de Pharmacologie, Université de Heidelberg, Allemagne.
Lebrun
C J
CJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000502:physiology* / Q000031:analogs & derivatives; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology*; D017257:Ramipril; D051381:Rats; D011918:Rats, Inbred SHR; 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
Inhibition de l'enzyme de conversion et cardioprotection: rôle des bradykinines.