MODULATION OF SYSTOLIC AND DIASTOLIC FUNCTION BY ENDOTHELIN-1 - RELATION TO CORONARY FLOW

Different conclusions have been reached with regard to the effect of endothelin (ET-1) on cardiac contractility. We examined systolic and diastolic function in response to constant known concentrations of ET-1 with or without ET-1 induced reductions in coronary flow (CF). Rat hearts (n = 21) were buffer-perfused using constant coronary flow (cCF) or constant perfusion pressure (cPP). Left ventricular function was assessed isovolumically. Addition of ET-1 (10(-9) M) in the cCF group caused a gradual increase in PP from 61+/-2 to 165+/-6 mmHg (mean+/-SE) (P < 0.01). Within 10 min left ventricular systolic pressure (LVSP) increased from 111+/-2 to a maximum of 134+/-4 mmHg (P < 0.01) and [LVdP/dt] increased from 1640+/-81 to a maximum of 2020+/-92 mmHg s(-1) (P < 0.01). After 15 min left ventricular end diastolic pressure (LVEDP), a measure of diastolic stiffness (DS), also increased. With ET-1 (10(-8) M), similar haemodynamic alterations appeared more rapidly. In the cPP group, ET-1 (10(-9) M) caused a sharp decrease in CF and LVSP fell from 115+/-8 to 62+/-12 mmHg at 10 min (P < 0.001). Systolic function remained stable at a reduced level for 1 h. DS did not change. Thus, ET-1 possesses positive inotropic effects and increases diastolic stiffness. Both effects may be masked by vasoconstriction-induced ischaemia.