Bradykinin pathway is involved in the acute hemodynamic effects of
enalaprilat in conscious dogs with heart failure.
Barbe;, Fabrice, Jin Bo Su; Thanh Tam Guyene; Bertrand Crozatier; Jol
M[umlaut]anard; Luc Hittinger.
Institut National de la Sant[umlaut]a et de la Recherche
M[umlaut]adicale (INSERM), Unit[umlaut]a 400, Facult[umlaut]a de
M[umlaut]adecine, 94010 Cr[umlaut]ateil and [alpha] Unit[umlaut]a
367, 75005 Paris, France
APStracts 2:0572H, 1995.
To determine the role of the renin-angiotensin system and the
bradykinin pathway in the mechanism of action of angiotensin
-converting enzyme inhibitors in heart failure, the acute effects of
enalaprilat (1 mg/kg) were compared with those of a renin inhibitor
(ciprokiren, 1mg/kg, iv) in 10 chronically instrumented conscious
dogs with heart failure induced by right ventricular pacing (3 weeks,
240 beats/min). The effects of enalaprilat and ciprokiren on
bradykinin infusion (3, 10, 30 g/min) and the effects of enalaprilat
in presence of the B2 bradykinin receptor antagonist HOE 140 (10
g/kg, iv) were also examined. Both inhibitors decreased significantly
mean aortic pressure (MAP) and increased cardiac output (CO).
However, enalaprilat induced significantly greater hemodynamic
effects than ciprokiren (MAP: -13 3 vs -6 1 mm Hg; CO: 0.4 0.1 vs
0.15 0.1 l/min). Bradykinin infusion lead to dose dependent decreases
in MAP and increases in CO which were not modified by a pretreatment
of ciprokiren but were potentiated tenfold by enalaprilat. HOE 140
reduced significantly the hemodynamic effects of enalaprilat. Thus,
endogenous bradykinin is involved in the acute hemodynamic effects of
enalaprilat in experimental heart failure.
Received 10 March 1995; accepted in final form 17 November 1995.
APS Manuscript Number H231-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95