Developmental conversion of inotropism by endothelin I and angiotensin II from positive to negative in mice

Inotropic effects on isolated neonatal and adult mouse myocardium of endoth elin I and angiotensin II were examined. Endothelin I produced a sustained positive inotropic response in the neonate but a sustained negative respons e in the adult. Both were concentration-dependent and were inhibited by the endothelin ETA receptor antagonist, BQ-123 (Cyclo(D-a-aspartyl-L-prolyl-D- valyl-L-leucyl-D-tryptophyl)). Angiotensin II produced a sustained positive inotropic response in the neonate while a sustained negative response in t he adult. Both were concentration-dependent and were inhibited by the angio tensin AT(i) receptor antagonist, YM358 (2,7-diethyl-5-((2'-(1H-tetrazol-5- yl) biphenyl-4-yl)methyl-5H-pyrazolo(1,5-b)(1,2,4)triazole potassium salt m onohydrate). These results indicate that inotropic responses of the mouse h eart to cardioactive peptides are unique among experimental animal species and may be reversed during development. (C) 1999 Elsevier Science B.V. All rights reserved.