HEMODYNAMIC AND INOTROPIC EFFECTS OF ENDOTHELIN-1 IN-VIVO

Endothelin-1 (ET-1) is known to have strong vasoactive properties. Con tradictory results have been reported with regard to its inotropic eff ects. This study examined the dose-dependent (500, 1000, 2500, 5000 an d 10000 ng ET-1/kg vs. NaCl controls) hemodynamic and inotropic effect s of ET-1 in 53 open-chest rats during and after a 7-min infusion. Bes ides measurements in the intact circulation the myocardial function wa s examined by isovolumic registrations independent of peripheral vascu lar effects. A transient ET-1 induced (500, 1000, 2500, 5000 ng ET-1/k g) decrease of the left ventricular systolic pressure (LVSP) and the m ean aortic pressure (AoP(mean)) was followed by a dose-related rise of these pressures (LVSP: -1%, -1%, +8%, +16% vs. preinfusion values; Ao P(mean): -11%, +9%, +39%, +52%). Heart rate (HR) was not influenced by ET-1. Due to the dose-dependent decrease of the stroke volume (SV) th e cardiac output (CO) was reduced (CO: -8%, -23%, -40%, -50%). After a n initial vasodilatation ET-1 elevates the total peripheral resistance (TPR: -1%, +49%, +139%, +215%) dose-dependently, 10000 ng ET-1/kg was a lethal dose resulting in cardiac failure within minutes (low output ). Since the maximum of the isovolumic LVSP (peak LVSP) and the corres ponding dP/dt(max) (peak dP/dt(max)) were unchanged under ET-1, the is ovolumic measurements do not indicate a positive inotropic effect of E T-1 in vivo in contrast to published results of in vitro experiments. It may be possible that a direct positive inotropic effect of ET-1 obs erved in in vitro studies is counterbalanced in vivo by an indirect ne gative inotropic effect due to the coronar-constrictive effect of ET-1 .