Captopril modifies the response of infarcted rat hearts to isoprenaline stimulation.
In this study the effect of the angiotensin converting enzyme (ACE) inhibitor captopril on beta-receptor responsiveness was investigated in failing rat hearts after experimental myocardial infarction. Infarcted rats were treated for 8 weeks with either captopril added to the drinking water (100 mg/kg/day; n = 5) or drinking water alone (n = 7). Treatment was started 2-3 days before myocardial infarction. A third group of untreated rats without myocardial infarction served as control (n = 6). At the end of the treatment period the hearts were perfused as described by Langendorff, and a cumulative dose-response curve of isoprenaline was obtained in each heart. In comparison with noninfarcted hearts, the response of heart rate and peak pressure rate (dP/dt) to isoprenaline stimulation was significantly depressed in hearts of infarcted rats. Chronic treatment with captopril significantly attenuated the reduced responsiveness to isoprenaline stimulation. This improved responsiveness in captopril-treated rat hearts might be due to prevention of "down-regulation" of myocardial beta-adrenoceptors. Other factors should also be considered, such as prevention of structural alterations in the noninfarcted myocardium, e.g., myocardial hypertrophy and fibrosis. Differences in infarct size did not play an important role, since infarct size was comparable in both groups of infarcted rats. This partial preservation of beta-adrenergic responsiveness was accompanied by a significant reduction in right ventricular weight and lung weight, suggesting that captopril also improved the signs of heart failure. Therefore, the results of this study indicate that early ACE inhibition in myocardial infarction may be useful in preventing deterioration of cardiac function.
van Wijngaarden
J
J
Department of Pharmacology and Clinical Pharmacology, University of Groningen, The Netherlands.
Monnink
S H
SH
Bartels
H
H
van Gilst
W H
WH
de Graeff
P A
PA
de Langen
C D
CD
Wesseling
H
H
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D007545:Isoproterenol