THE EFFECT OF INTRAARTERIAL ENDOTHELIN ON RESTING BLOOD-FLOW AND SYMPATHETICALLY MEDIATED VASOCONSTRICTION IN THE FOREARM OF MAN

1 The hypothesis that endothelin (ET) influences sympathetically mediated vasoconstriction was investigated in 13 healthy, male subjects. 2 ET (1 pmol min-1) was infused for 60 min into the left brachial arteries of seven healthy male subjects. Resting forearm blood flow, and sympathetic vasoconstriction produced by lower body negative pressure (LBNP; 15 mm Hg), was measured in both arms by strain gauge plethysmography. In a further six subjects, noradrenaline (NA) was infused intra-arterially at doses of 150-600 pmol min-1, with and without co-infusion of ET (1 pmol min-1), with blood flow measured in both forearms. 3 ET produced a small but significant reduction of blood flow in the infused forearm from 3.9 +/- 0.6 ml 100 ml-1 min-1 during infusion of saline, to 3.3 +/- 0.7 ml 100 ml-1 min-1 during infusion of ET at 60 min (P < 0.05). Blood flow in the non-infused forearm was not altered by ET infusion. 4 NA produced a significant and dose-dependent reduction of blood flow in the infused forearm, from 3.13 +/- 0.5 ml 100 ml-1 min-1 during saline infusion, to 1.49 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1 (P < 0.001). During co-infusion of ET, blood flow was reduced similarly in the infused arm from 3.15 +/- 0.7 ml 100 ml-1 min-1 during saline infusion to 1.55 +/- 0.2 ml 100 ml-1 min-1 with NA at 600 pmol min-1. Blood flow in the non-infused arm was not altered by ET and NA infusion. 5 During saline infusion, LBNP reduced blood flow in the infused and non-infused forearms from 3.9 +/- 0.6 to 3.0 +/- 0.4, and from 4.5 +/- 0.6 to 3.2 +/- 0.5 ml 100 ml-1 min-1 respectively. Following ET for 60 min, blood flow in the infused and non-infused forearms was similarly reduced by LBNP, from 3.3 +/- 0.7 to 2.5 +/- 0.4, and from 4.7 +/- 1.2 to 3.6 +/- 0.7 ml 100 ml-1 min-1 respectively. Infusion of ET did not affect responses to LBNP. 6 We conclude that ET is a potent vasoconstrictor of resistance vessels in the forearm circulation in man, producing a slowly progressive effect which is unique among the known constrictor agents and supports a role for ET in long-term maintenance of vascular tone. Intra-arterial ET does not, however, appear to affect NA or sympathetically (LBNP) mediated vasoconstriction in the human forearm.