Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril.

H Buikema; D J van Veldhuisen; H Hegeman; W H van Gilst

doi:10.1016/s1071-9164(97)90046-4

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Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril.

H Buikema·D J van Veldhuisen·H Hegeman·W H van Gilst

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Abstract

BACKGROUND: Endothelial function is progressively disturbed after myocardial infarction (MI), which may be related to both neurohumoral activation and hemodynamic alterations. Consequently, it may be suggested that drugs that favorably affect these factors may also have a positive effect on endothelial function. METHODS AND RESULTS: Rats underwent coronary ligation (n = 24) or remained unoperated (n = 21), and were randomized to captopril (25 mg/kg/d) or ibopamine (10 mg/kg/d) or remained untreated. Treatment was started following MI and lasted 8 weeks, after which rats were sacrificed for in vitro studies. Left ventricular end-systolic pressure was higher in rats treated with captopril (83 +/- 6 mmHg) and ibopamine (80 +/- 3 mmHg), as compared with untreated MI rats (48 +/- 6 mmHg, P < .01 for both). Increased plasma norepinephrine levels in MI rats were reduced by captopril and ibopamine (both P < .05). Infarct size was smaller in rats treated with captopril (26.7 +/- 3.6%, P < .05) and ibopamine (31.4 +/- 4.3%, P = NS), as compared with untreated rats (41.7 +/- 2.4%). Maximal endothelium-dependent relaxation (Emax; % precontraction) and the concentration of methacholine causing 50% Emax, expressed as negative log(pIC50) were significantly reduced in aortic rings from MI control subjects (pIC50 = 6.15 +/- 0.06 mol/L, Emax = 32.0 +/- 4.2%), as compared with normal control subjects (pIC50 = 6.57 +/- 0.07 mol/L, P < .001; Emax = 50.0 +/- 4.9%, P = .022). Captopril (pIC50 = 6.30 +/- 0.08 mol/L, Emax = 45.1 +/- 7.0%) and ibopamine (pIC50 = 6.60 +/- 0.08 mol/L, Emax = 43.8 +/- 5.2%) improved these parameters in MI rats. CONCLUSION: The results demonstrate preservation of endothelial function by early pharmacologic intervention after experimental MI in rats in the setting of concomitant reduction in infarct size.

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Animals Captopril Cardiotonic Agents Deoxyepinephrine Endothelium, Vascular Hemodynamics Male Myocardial Infarction Norepinephrine Rats Rats, Wistar Vasodilator Agents Journal Article Research Support, Non-U.S. Gov't

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H Buikema, D J van Veldhuisen, H Hegeman, W H van Gilst. 1997. Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril.. https://doi.org/10.1016/s1071-9164(97)90046-4

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