Impairment of the nitric oxide–mediated vasodilator response to mental stress in hypertensive but not in hypercholesterolemic patients

Objectives. This study investigated whether mental stress–induced vasodilation mediated by endothelium-derived nitric oxide (NO) is defective in conditions with endothelial dysfunction, such as hypertension and hypercholesterolemia. Background. Vascular release of NO modulates the vasodilator response to mental stress in healthy subjects. Previous studies have shown that hypertensive and hypercholesterolemic patients have impaired endothelium-dependent vasodilation to pharmacologic agents due to decreased NO activity. However, whether this abnormality also operates in response to physiologic stimuli such as mental stress has not been defined. Methods. Forearm blood flow responses (plethysmography) to mental stress were compared in 12 normal subjects, 12 hypertensive patients and 10 hypercholesterolemic patients before and during NO synthesis inhibition with NG-monomethyl-l-arginine (4 μmol/min). Vascular responses to acetylcholine (7.5, 15 and 30 μg/min), an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 μg/min), an exogenous NO donor, were also assessed in each group. Results. During saline the vasodilator response to mental stress was significantly blunted in hypertensive (37 ± 11%; p = 0.01) but not in hypercholesterolemic (85 ± 21%; p = 0.78) patients compared with controls (93 ± 15%). NG-Monomethyl-l-arginine administration significantly blunted mental stress–induced vasodilation in healthy subjects (p = 0.004 vs. saline) and hypercholesterolemic patients (p = 0.03 vs. saline), but not in hypertensive patients (p = 0.69 vs. saline). The vasodilator effect of the highest dose of acetylcholine was similarly blunted in hypertensive (215 ± 44%; p = 0.02) and hypercholesterolemic (172 ± 71%; p = 0.02) patients compared with controls (364 ± 34), whereas the vasorelaxing response to sodium nitroprusside was similar in the three groups. Conclusions. Hypertensive but not hypercholesterolemic patients have impaired NO-dependent vasodilation during mental stress. These findings may be accounted for by different mechanisms underlying endothelial dysfunction in these two conditions and might explain an increased susceptibility of hypertensive patients to vascular damage over repeated exposure to stressful situations.