Intra-arterial infusion of endothelin-1 in humans caused dose-dependent decreases in forearm blood flow of 25-42%, and at a higher dose elicited severe adverse reactions including pain and edema.
What are the regional haemodynamic effects and adverse reactions of endothelin-1 infusion in humans and rats?
Endothelin-1 infusion causes significant regional vasoconstriction and at high doses induces severe adverse effects including pain and edema due to increased capillary hydrostatic pressure.
Endothelin-1 was infused into the non-dominant brachial artery in two male subjects. We then monitored intra-arterial mean blood pressure, right atrial pressure, the heart rate and forearm blood flow (by plethysmography). Endothelin-1 at a dose of 5 x 10(-14) to 5 x 10(-9) mol, infused over 5 min periods, elicited no major changes in mean arterial pressure, heart rate and right atrial pressure. We observed an initial increase in forearm blood flow, followed by dose-dependent decreases of 25, 34 and 42% at 5 x 10(-11) to 5 x 10(-9) mol. A higher dose of endothelin-1, 5 x 10(-8) mol, given to only one of the subjects, elicited sweating and vomiting. In this subject, mean arterial pressure, right atrial pressure and the heart rate did not change, while forearm blood flow increased transiently. A deep muscular pain developed in the forearm receiving the endothelin-1 infusion after 30 min (maximum 2 h, duration 10 h), and this pain was intensified by touch and muscle contractions. The force of muscle contractions in the forearm was markedly reduced and a visible oedema developed. In order to investigate the mechanisms of oedema formation, endothelin-1 (10(-10) to 5 x 10(-8) mol/l) was given intra-arterially in a rat hindquarter preparation which was perfused at a constant flow rate. In the rat, endothelin-1 increased both pre- and postcapillary resistance, leading to an increase in capillary hydrostatic pressure and a marked net transcapillary fluid transfer from the perfusate to tissue. There was no sign of increased vascular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Dahlöf et al. (Sat,) reported a other. Endothelin-1 was evaluated on Forearm blood flow. Intra-arterial infusion of endothelin-1 in humans caused dose-dependent decreases in forearm blood flow of 25-42%, and at a higher dose elicited severe adverse reactions including pain and edema.