EFFECTS OF ENDOTHELIN-1 ON ARTERIAL AND VENOUS RESISTANCES IN ANESTHETIZED RATS

The effects of endothelin-1 and vehicle (0.9% NaCl) on mean arterial p ressure, heart rate, mean circulatory filling pressure, systemic arter ial resistance, cardiac output and venous resistance were studied in f our groups of pentobarbitone-anaesthetized rats, either in presence or absence of phentolamine. I.v. bolus injections of endothelin-l at 0.5 , 1 and 2 nmol/kg dose dependently increased mean arterial pressure (2 2, 34 and 40 mmHg), arterial resistance (33, 93 and 122% over baseline ), venous resistance (40, 117 and 143% over baseline) and mean circula tory filling pressure (1.0, 1.7 and 1.8 mmHg), but decreased heart rat e(-16, -21 and -17 beats/min) and cardiac output (-6, -28 and -35% bel ow baseline). The vehicle did not significantly alter any of these var iables. During the continuous infusion of phentolamine (300 mu g/kg pe r min), endothelin-l caused similar increases in arterial resistance, venous resistance and mean circulatory filling pressure, similar reduc tion in cardiac output but significantly greater presser and bradycard ic responses, suggesting that the arterial and venous constrictor effe cts of endothelin-l are not due to sympathetic activation and the stim ulation of alpha-adrenoceptors. The results show that endothelin-l rai sed mean arterial pressure via the increment in systemic arterial resi stance, since cardiac output was markedly reduced. This decrease in ca rdiac output was mediated by increases in arterial as well as venous r esistances. The vasoconstrictor and venoconstrictor effects of endothe lin-l were independent of sympathetic tone.