Role of bradykinin in the antihypertrophic effects of enalapril in the newborn pig heart.
Rapid growth of the left ventricle of the newborn pig heart can be restrained by treating piglets with the angiotensin converting enzyme inhibitor, enalapril maleate. This reduced rate of growth is reflected in vitro by reduced rates of ribosome formation and protein synthesis, and may be due to decreased availability of angiotensin II (AII), a potentially hypertrophic agent; decreased numbers of AII receptors; increased availability of bradykinin, a potentially antihypertrophic agent; or reduced hemodynamic load on the left ventricle. Because enalapril decreases degradation of bradykinin, the role of bradykinin as an inhibitor of cardiac growth in the newborn heart was investigated. Addition of 1 x 10(-5) M bradykinin and 1 x 10(-6) M enalapril to the perfusate of isolated hearts from 2 day old piglets did not significantly alter heart rate, contents of ATP or creatine phosphate or rates of ribosome formation or protein synthesis during 1 h of perfusion. Similarly, exposure of myocytes isolated from the left ventricular free wall of piglets to 5 x 10(-6) M bradykinin for 72 h did not alter the rate of [3H]-phenylalanine incorporation into total protein. The reduced rate of left ventricular growth in vivo caused by enalapril administration was not reversed by simultaneous treatment with the specific bradykinin receptor antagonist, HOE 140. HOE 140 alone did not alter ventricular growth as compared to hearts from untreated piglets. In summary, these results demonstrate that the reduced rate of left ventricular growth in vivo and the reduced rate of ribosome formation and protein synthesis in the left ventricle in vitro after enalapril treatment of piglets is not the result of an inhibitory effect of bradykinin on cardiac growth.
Beinlich
C J
CJ
Weis Center for Research, Geisinger Clinic, Danville, PA 18722, USA.
Rissinger
C J
CJ
Vitkauskas
K J
KJ
Morgan
H E
HE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006332:Cardiomegaly / Q000517:prevention & control; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine
D010725:Phosphocreatine; D004656:Enalapril; C065679:icatibant; D000255:Adenosine Triphosphate; D001920:Bradykinin