The importance of endothelin-1 (ET-1) in the pathophysiology of essential hypertension is unclear. We therefore compared the effects of endothelin ETA receptor blockade and the stimulation of ETA and ETB 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 ETA 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 ETA and ETB 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 ETB 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 ETA receptor in this condition.

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