TY - JOUR
T1 - Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats
T2 - Effects of ibopamine and captopril
AU - Buikema, Hendrik
AU - van Veldhuisen, Dirk J.
AU - Hegeman, Han
AU - van Gilst, Wiek H.
N1 - Funding Information:
Supported by Bristol-Myers Squibb BV, Woerden, The Netherlands, and Zambon Research SpA, Milau, Italy. Manuscript received Oct. 11, 1996; revised manuscript received Feb. 19, 1997; revised manuscript accepted March 4, 1997. Reprint requests: Hendrik Buikema, PhD, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. Some of the results in this study have been previously reported in J Cardiovascular Pharmacol 1994;24:171-4 and are published with permission. © 1997 Churchill Livingstone Inc.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Chronic heart failure
KW - Endothelium-dependent relaxation
KW - Methacholine
UR - http://www.scopus.com/inward/record.url?scp=0031158966&partnerID=8YFLogxK
U2 - 10.1016/S1071-9164(97)90046-4
DO - 10.1016/S1071-9164(97)90046-4
M3 - Article
C2 - 9220312
AN - SCOPUS:0031158966
SN - 1071-9164
VL - 3
SP - 125
EP - 132
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 2
ER -