EFFECTS OF ANGIOTENSIN-II AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON HUMAN MYOCARDIUM

Human myocardial angiotensin II receptors and the angiotensin AT(1) an d AT(2) receptor subtypes were characterised using the partial angiote nsin II receptor agonist [I-125][Sar(1),IIe(8)]angiotensin II and the selective antagonists losartan (1H-tetrazol-5-yl)biphenyl-4-yl)-methyl ]imidazole) and PD 123177 3-methylphenyl)methyl]-5-(diphenyl-acetyl)-4 ,5,6,7 tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid). The d ensity of angiotensin II receptors was higher in atrial than in ventri cular myocardium. Angiotensin AT(2) receptors were predominant in atri a and ventricles (80-85% of total angiotensin II receptors). Only in i solated, electrically driven atrial trabeculae but not in ventricular preparations, angiotensin II did produce a concentration-dependent pos itive inotropic effect, which was antagonized exclusively by the angio tensin AT(1) receptor antagonist losartan and which amounted to about 20% of the positive inotropic effect of milrinone and isoprenaline. Th e application of the angiotensin-converting enzyme inhibitors captopri l, enalaprilat and ramiprilat had no inotropic effect in either tissue . It is concluded that angiotensin AT(1) receptors exclusively mediate direct positive inotropic effects in atrial myocardium. Since angiote nsin-converting enzyme inhibitors do not produce any inotropic effect, tonic regulation of basal force of contraction by angiotensin II does not occur.