Contributions Biological Activity of Angiotensin-( l7 ) Heptapeptide in the Hamster Heart

Angiotensin II has been reported to have both a positive inotropic effect and a coronary constrictor action in the hamster heart. To study the contribution to these responses of phenylalanine in position 8, we assessed the direct cardiac effects of angiotensin-(l-7), which lacks phenylalanine in position 8. Syrian hamsters were used to determine the effects of angiotensin-(1-7) on cardiac performance in the diseased and normal hearts. We used the isolated isovolumic heart preparation perfused either at a constant pressure of 50 mm Hg or at a constant coronary (myocardial) flow rate of 7 ml/min (seven cardiomyopathic hamsters [CMH] and seven normal hamsters [NH] in each subgroup). At constant perfusion pressure, coronary (myocardial) flow rate decreased (/?<0.01) in both CMH and NH (-31 ±8% vs. 3 9 ± 4 % of baseline, respectively); but the percent decrease in left ventricular pressure and the first derivative of left ventricular pressure over time (LV +dP/dt) was significant only in NH ( 8 ± 1 % and -9±4%) but not in CMH (-14±5% and -21±8%). On the other hand, at a constant coronary (myocardial) flow rate, left ventricular pressure and LV +dP/dt tended to increase in both CMH and NH (+10±3% and +6±2% of baseline vs. +7±7% and +7±5%, respectively) but these changes were not significant. In comparison, angiotensin II, given under the same conditions of constant coronary (myocardial) flow rate, increased left ventricular pressure and LV +dP/dt in both CMH and NH (65±12% and 71±11% of baseline vs. 155±84% and 119±50%, respectively; ra=3, in each subgroup). Data suggest that, in the hamster heart, angiotensin-(l-7) has 1) a selective coronary vasoconstrictor effect and 2) no significant direct positive inotropic action that can be related to the absence of phenylalanine in position 8. (Hypertension 1990;15(suppl I):I-29-I-33)