ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE ABNORMAL ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION OF PATIENTS WITH ESSENTIAL-HYPERTENSION

Background. Patients with essential hypertension have abnormal endothelium-dependent vasodilation. Because the endothelium exerts its action on the vascular smooth muscle through the release of several substances, it is important to identify which of these factors is involved in the abnormal response of hypertensive arteries. Methods and Results. To investigate the role of endothelium-derived nitric oxide in this abnormality, we studied the vascular effect of the arginine analogue N(G)-monomethyl-L-arginine, an inhibitor of the endothelial synthesis of nitric oxide, under baseline conditions and during infusion of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, a direct smooth muscle dilator. The study included 11 hypertensive patients (seven men; age, 46.5+/-9 years) and 10 normal control subjects (seven men; age, 45.7+/-7 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood How was similar in normal control subjects and hypertensive patients (2.97+/-0.7 versus 2.86+/-1.1 mL . min-1 . 100 mL-1, respectively). N(G)-monomethyl-L-arginine produced a significantly greater decrease in blood flow in control subjects than in patients (1.08+/-0.6 versus 0.32+/-0.4 mL . min-1 . 100 mL-1; p < 0.004). The vasodilator response to acetylcholine was reduced in patients compared with control subjects (maximum flow, 8.2+/-4 versus 16.4+/-8 mL . min-1 . 100 mL-1; p<0.001). N(G)-monomethyl-L-arginine blunted the vasodilator response to acetylcholine in control subjects (maximum flow decreased from 16.4+/-8 to 7.01+/-3 mL . min-1 . 100 mL-1; p<0.004); however, the arginine analogue did not significantly alter the response to acetylcholine in hypertensive patients (maximum flow, 8.2+/-4 versus 8.01+/-5 mL . min-1 . 100 mL-1). N(G)-monomethyl-L-arginine did not modify the vasodilator response to sodium nitroprusside in either control subjects or patients. Conclusions. These findings indicate that patients with essential hypertension have a defect in the endothelium-derived nitric oxide system that may at least partly account for both the increased vascular resistance under basal conditions and the impaired response to endothelium-dependent vasodilators.