Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension

Patients with essential hypertension are characterized by impaired basal an d agonist-evoked nitric oxide release and increased endogenous endothelin ( ET)-1-induced vasoconstriction. To assess whether candesartan, an angiotens in II type 1 receptor blocker, can improve endothelial function, we studied the changes in forearm blood flow (FBF) induced in 15 hypertensive patient s and in 15 control subjects by the intrabrachial infusion of N-G-monomethy l-L-arginine (L-NMMA), norepinephrine, the ET A/B receptor antagonist TAK 0 44, sodium nitroprusside, and acetylcholine. In hypertensive patients, the FBF study was repeated 2 and 12 months after the start of treatment with ca ndesartan cilexetil (8 to 16 mg daily). Compared with controls (maximal FBF decrease, -46+/-11%), hypertensive patients showed a reduced (P<0.001) vas oconstrictor response to L-NMMA (maximal FBF decrease, -28+/-7%); the respo nse to norepinephrine was only slightly impaired, and the response to sodiu m nitroprusside was similar to that of controls. Finally, TAK-044 caused gr eater vasodilation in hypertensive patients (maximal FBF increase, 77+/-9%) than in controls (maximal FBF increase, 17+/-10%). In hypertensive patient s, candesartan cilexetil significantly enhanced vasoconstriction to L-NMMA after 2 and 12 months (maximal FBF decrease, 37+/-2% [P<0.05] and 42+/-2% [ P<0.001], respectively). The responses to norepinephrine, acetylcholine, an d sodium nitroprusside were not modified after 2 months. After 12 months, t he responses to acetylcholine and sodium nitroprusside were significantly ( P<0.05) enhanced at the highest rates. Vasodilation to TAK-044 was abolishe d after treatment with candesartan cilexetil; this effect is associated wit h a reduced plasma ET-1 concentration. This study demonstrated that the ang iotensin II receptor blocker candesartan improves tonic nitric oxide releas e and reduces vasoconstriction to endogenous ET-1 in the forearm of hyperte nsive patients.