Captopril protects against myocardial injury induced by magnesium deficiency.
We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.
Freedman
A M
AM
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Cassidy
M M
MM
Weglicki
W B
WB
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D006224:Cricetinae; D003936:Diagnosis, Computer-Assisted; D015773:Enalaprilat / Q000494:pharmacology; D008275:Magnesium Deficiency / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000473:pathology
D000959:Antihypertensive Agents; C044958:zofenopril; D002216:Captopril; D015773:Enalaprilat