Issues surrounding a local cardiac renin system and the beneficial actions of angiotensin-converting enzyme inhibitors in ischemic myocardium.
Several experimental in vitro and in vivo studies have shown that structurally diverse converting enzyme inhibitors improve contractile dysfunction, as well as reduce arrhythmia production and acute mortality after occlusion of the coronary artery. Biochemical data have demonstrated that some inhibitors of converting enzyme bind better to cardiac angiotensin-converting enzyme (ACE) than others; however, there has not been any demonstrated correlation between inhibition of the enzyme and improvement in cardiac physiology in the acutely dysfunctioning stunned myocardium. It is assumed that ACE inhibitors reduce tissue generation of angiotensin II; however, this relationship as well as peptide levels in coronary venous effluent need to be specifically measured. The multiple substrates of ACE necessitate further work to explore the role of bradykinin and prostacyclin, which have been implicated by some workers as contributing to the beneficial action of ACE inhibitors. A new question is whether sulfhydryl-containing ACE inhibitors are scavengers of toxic free radicals. Captopril, e.g., has been shown to be a free radical scavenger in superoxide-generating systems. Further work is required; however, as one report has recently shown, captopril does not directly scavenge superoxide but acts indirectly as an antioxidant or by altering the concentration of cytochrome c.
Sweet
C S
CS
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy*; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II