Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications.
Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D007276:Injections, Intraventricular; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D017257:Ramipril; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects; D014018:Tissue Distribution
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D004656:Enalapril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril