Vasostatins exert negative inotropism in the working heart of the frog

An in vitro isolated working frog heart (Rana esculenta) was used to study the effects of exogenous CGA(1-76) (vasostatin 1), CGA(1-113) (vasostatin 2), and the synthetic CGA(7-57) on cardiac performance. Under basal cardiac conditions, the dose-response curves of the three peptides from 10(-8) to 10(-7) M showed a significant calcium-dependent negative inotropism that involved neither the endocardial endothelium nor the adrenergic and muscarinic receptors. In addition, the CgA fragments clearly counteracted the typical positive inotropism of isoprenaline (10(-9) M). Taken together, these results provide the first evidence for a cardio-suppressive role for the vasostatins.