Preservation of left ventricular function and coronary flow by angiotensin I-converting enzyme inhibition in the hypertensive-diabetic Dahl rat.
The effect of the angiotensin I-converting enzyme (ACE) inhibitor benazepril (55 mg/kg orally) on the preservation of cardiac performance in diabetic-hypertensive Dahl S rats was investigated. Diabetes mellitus was produced by streptozotocin. Fasting (4-h) blood glucose levels were 279 +/- 50 mg/dL in diabetic Dahl salt-sensitive v 79 +/- 5 mg/dL in nondiabetic Dahl salt-sensitive rats. Cardiac performance was determined at the end of 8 weeks in an isolated perfused working heart apparatus. Peak left ventricular pressure (LVPmax), left ventricular peak negative dP/dt, and coronary flow were depressed in diabetic Dahl S rats (P < or = .05 v control). These deficits in cardiac function were not observed in diabetic Dahl S rats chronically treated with benazepril. The beneficial effects of benazepril apparently were independent of systolic blood pressure reduction. Although plasma ACE activity was increased in diabetic Dahl S rats, plasma renin activity was reduced. This suggests that the beneficial effects of ACE inhibition may be due to an effect upon the kinin system rather than the renin-angiotensin system. The benazepril-associated preservation of cardiac function in this study suggests that ACE inhibitors may be beneficial in the treatment of diabetic heart disease.
Given
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MB
Department of Medicine, Louisiana State University School of Medicine at New Orleans 70112.
Lowe
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Gelvin
C R
CR
Sander
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GE
Giles
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TD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D013311:Streptozocin; D016277:Ventricular Function, Left / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D012083:Renin; C044946:benazepril