The renin-angiotensin system during acute myocardial ischemia in dogs.
We used the technique of high-performance liquid chromatography combined with radioimmunoassay to establish the profile of angiotensin peptides in the periphery and across the circulation of the dog's heart. Data were obtained before and after blockade of angiotensin converting enzyme, and after acute myocardial ischemia produced by occlusion of the left anterior descending coronary artery. Baseline values of plasma renin activity and immunoreactive angiotensin II were higher in the aortic root than in the coronary sinus but concentrations of angiotensin I and angiotensin-(1-7) were similar. In untreated animals, coronary occlusion produced significant increases in renin activity and arterial and venous levels of angiotensin I and angiotensin II. Inhibition of converting enzyme with benazeprilat (CGS-14,831) increased baseline circulating levels of angiotensin I, whereas angiotensin II and its carboxyl terminal fragments were reduced markedly. Baseline plasma levels of angiotensin-(1-7) and its fragments did not change. Myocardial ischemia in benazeprilat-treated dogs increased plasma renin activity and circulating levels of angiotensin I. Concentrations of angiotensin II and angiotensin-(1-7) did not change either in peripheral blood or across the coronary circulation. These results indicate that angiotensin peptides can be formed endogenously by enzymatic pathways alternate to converting enzyme. Furthermore, these data provide the basis for a further understanding of the role of the renin-angiotensin system after myocardial ischemia.
Santos
R A
RA
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5070.
Brum
J M
JM
Brosnihan
K B
KB
Ferrario
C M
CM
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000097:blood / Q000145:classification; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000097:blood*; D004285:Dogs; D008297:Male; D009994:Osmolar Concentration; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D001552:Benzazepines; D012083:Renin; C052133:benazeprilat