Effect of the Angiotensin II Type 1 Receptor Blocker Candesartan on Endothelial Function in Patients With Essential Hypertension

Abstract

Abstract —Patients with essential hypertension are characterized by impaired basal and agonist-evoked nitric oxide release and increased endogenous endothelin (ET)-1–induced vasoconstriction. To assess whether candesartan, an angiotensin II type 1 receptor blocker, can improve endothelial function, we studied the changes in forearm blood flow (FBF) induced in 15 hypertensive patients and in 15 control subjects by the intrabrachial infusion of N G -monomethyl- l -arginine (L-NMMA), norepinephrine, the ET A/B receptor antagonist TAK 044, sodium nitroprusside, and acetylcholine. In hypertensive patients, the FBF study was repeated 2 and 12 months after the start of treatment with candesartan cilexetil (8 to 16 mg daily). Compared with controls (maximal FBF decrease, −46±11%), hypertensive patients showed a reduced ( P <0.001) vasoconstrictor response to L-NMMA (maximal FBF decrease, −28±7%); the response to norepinephrine was only slightly impaired, and the response to sodium nitroprusside was similar to that of controls. Finally, TAK-044 caused greater vasodilation in hypertensive patients (maximal FBF increase, 77±9%) than in controls (maximal FBF increase, 17±10%). In hypertensive patients, 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, and sodium nitroprusside were not modified after 2 months. After 12 months, the responses to acetylcholine and sodium nitroprusside were significantly ( P <0.05) enhanced at the highest rates. Vasodilation to TAK-044 was abolished after treatment with candesartan cilexetil; this effect is associated with a reduced plasma ET-1 concentration. This study demonstrated that the angiotensin II receptor blocker candesartan improves tonic nitric oxide release and reduces vasoconstriction to endogenous ET-1 in the forearm of hypertensive patients.