Effects of endothelin-1 on arterial and venous resistances in anaesthetized rats

The effects of endothelin-1 and vehicle (0.9% NaCl) on mean arterial pressure, heart rate, mean circulatory filling pressure, systemic arterial resistance, cardiac output and venous resistance were studied in four groups of pentobarbitone-anaesthetized rats, either in presence or absence of phentolamine. I.v. bolus injections of endothelin-1 at 0.5, 1 and 2 nmol/kg dose dependently increased mean arterial pressure (22, 34 and 40 mmHg), arterial resistance (33, 93 and 122% over baseline), venous resistance (40, 117 and 143% over baseline) and mean circulatory filling pressure (1.0, 1.7 and 1.8 mmHg), but decreased heart rate (-16, -21 and -17 beats/min) and cardiac output (-6, -28 and -35% below baseline). The vehicle did not significantly alter any of these variables. During the continuous infusion of phentolamine (300 microg/kg per min), endothelin-1 caused similar increases in arterial resistance, venous resistance and mean circulatory filling pressure, similar reduction in cardiac output but significantly greater pressor and bradycardic responses, suggesting that the arterial and venous constrictor effects of endothelin-1 are not due to sympathetic activation and the stimulation of alpha-adrenoceptors. The results show that endothelin-1 raised mean arterial pressure via the increment in systemic arterial resistance, since cardiac output was markedly reduced. This decrease in cardiac output was mediated by increases in arterial as well as venous resistances. The vasoconstrictor and venoconstrictor effects of endothelin-1 were independent of sympathetic tone.