Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension

The importance of endothelin-1 (ET-1) in the pathophysiology of essential hypertension is unclear. We therefore compared the effects of endothelin ET_A receptor blockade and the stimulation of ET_A and ET_B receptors, and their interaction with the sympathetic nervous system, in the forearm resistance vessels of patients with essential hypertension and healthy control subjects. A total of 27 untreated patients with essential hypertension (blood pressure >160/100mmHg) and 25 normotensive (blood pressure <140/90mmHg) age- and sex-matched control subjects participated in these studies. A total of 10 patients and 10 controls took part in each phase. Locally active doses of study drugs were infused into the non-dominant brachial artery, while forearm blood flow was measured by venous occlusion plethysmography. A 60min infusion of BQ-123 (an ET_A receptor antagonist; 100nmol/min) significantly increased forearm blood flow by 40±8% in hypertensive patients and by 35±5% in controls, with no difference between groups (P = 0.49). Forearm vasoconstriction to ET-1 (an ET_A and ET_B receptor agonist; 5 pmol/min) for 90min was significantly blunted in hypertensive patients (21±4%) compared with control subjects (37±3%; P = 0.0001). Forearm vasoconstriction to sarafotoxin S6c (an ET_B receptor agonist; 10 pmol/min) for 90min was similar in hypertensive patients (44±5%) and control subjects (48±4%; P = 0.95). Sympathetically mediated vasoconstriction produced by lower-body negative pressure was not different in hypertensive patients compared with controls, and was not affected by infusion of ET-1 or sarafotoxin S6c. There were no differences in the observed increase in forearm blood flow with a control vasodilator (sodium nitroprusside) or the observed decrease in forearm blood flow with a control vasoconstrictor (noradrenaline) between hypertensive patients and control subjects. BQ-123 produced a significant increase in forearm blood flow in hypertensive patients, consistent with the anti-hypertensive actions of this agent. In conclusion, forearm vasoconstriction to ET-1, but not to sarafotoxin S6c, was reduced in patients with essential hypertension, consistent with possible down-regulation of the ET_A receptor in this condition.