Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries.
We investigated the preventive effects of long-term treatment with the angiotensin converting enzyme inhibitor ramipril on myocardial left ventricular hypertrophy and capillary length density in spontaneously hypertensive rats. Rats were treated in utero and subsequently up to 20 weeks of age with a high dose (1 mg/kg per day) or with a low dose (0.01 mg/kg per day) of ramipril. Animals given a high dose of ramipril remained normotensive, whereas those given a low dose developed hypertension in parallel to vehicle-treated controls. At the end of the treatment period, converting enzyme activity in heart tissue was inhibited dose-dependently in the treated groups. Both groups revealed an increase in myocardial capillary length density together with increased myocardial glycogen and reduced citric acid concentrations. Left ventricular mass was reduced only in high dose- but not in low dose-treated animals. Our results demonstrate that early onset treatment with a converting enzyme inhibitor can induce myocardial capillary proliferation, even at doses too low to antagonize the development of hypertension or left ventricular hypertrophy. We hypothesize that potentiation of kinins is responsible for this effect, probably by augmenting myocardial blood flow, which is a well-known trigger mechanism of angiogenesis in the heart.
Unger
T
T
Department of Pharmacology, University of Heidelberg, Frankfurt/Main, FRG.
Mattfeldt
T
T
Lamberty
V
V
Bock
P
P
Mall
G
G
Linz
W
W
Schölkens
B A
BA
Gohlke
P
P
D000284:Administration, Oral; D000367:Age Factors; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002312:Cardiomyopathy, Hypertrophic / Q000517:prevention & control*; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy*; D006984:Hypertrophy; D008431:Maternal-Fetal Exchange; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D011247:Pregnancy; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D002951:Citrates; D019343:Citric Acid; D006003:Glycogen; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril