Influence of angiotensin-converting enzyme inhibition by fosinopril on myocardial perfusion in streptozotocin-diabetic rats.
We examined the influence of the new angiotensin-converting enzyme inhibitor (ACEI) fosinopril on function and perfusion of the diabetic rat heart. Streptozotocin-diabetic rats (60 mg/kg body weight) were treated with fosinopril (10 mg/kg body weight/day) for 4 months. Cardiac performance was analyzed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring epicardial fluorescence changes after injection of FITC-dextrane (3 kDa) as described previously. As compared with controls, fosinopril prevented or diminished the increase in end-diastolic pressure (EDP), coronary perfusion pressure (CPP), and vascular resistance in diabetes. The intravascular volume strongly reduced in diabetes was increased, and the epicardial perfusion rate was accelerated in hearts of diabetic rats treated with fosinopril. The vascular exchange diminished in hearts of untreated diabetic rats was enhanced, and the transcapillary permeability was slightly accelerated at low flow rates. These data indicate that treatment of streptozotocin-diabetic rats with fosinopril prevents severe disturbances of coronary autoregulation and at least partly the impairment of cardiac perfusion generally observed in diabetic rats. Together with previously published morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats with fosinopril, our observations suggest that ACE inhibition by fosinopril is cardioprotective in diabetes.
Rösen
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P
Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany.
Rump
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AF
Rösen
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D017328:Fosinopril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D013311:Streptozocin; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D013311:Streptozocin; D017328:Fosinopril