Hypertension, Vol 23, 411-418, Copyright © 1994 by American Heart Association
P Gohlke, W Linz, BA Scholkens, I Kuwer, S Bartenbach, A Schnell and T Unger
The effect of chronic low- and high-dose treatment with the angiotensin-
converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on
the development of hypertension and left ventricular hypertrophy as well as
on functional and biochemical alterations of the heart was studied in
stroke-prone spontaneously hypertensive rats treated prenatally and
subsequently up to the age of 20 weeks. The contribution of endogenous
bradykinin potentiation to the ACE inhibitor actions was assessed by
cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500
micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose
ACE inhibitor treatment prevented the development of hypertension and left
ventricular hypertrophy. Chronic bradykinin receptor blockade did not
attenuate the antihypertensive and antihypertrophic actions of ramipril.
High-dose ramipril treatment improved cardiac function, as demonstrated by
an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and
coronary flow (22.1%), without a change in heart rate. The activities of
lactate dehydrogenase and creatine kinase and lactate concentration in the
coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively.
Myocardial tissue concentrations of glycogen and the energy-rich phosphates
ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%,
respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE
inhibitor treatment led to a pattern of changes in cardiodynamics and
cardiac metabolism similar to that observed with the high dose. All ACE
inhibitor-induced effects on cardiac function and metabolism were abolished
by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin
Department of Pharmacology, Christian Albrechts University of Kiel, Germany.
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