We have previously shown that patients with essential hypertension have impaired endothelium-dependent vascular relaxation. In a separate investigation, we demonstrated that increased availability of precursor for endothelium-derived nitric oxide is rate-limiting and can potentiate the response to endothelium-dependent vasodilators in normal humans. The present study was undertaken to determine whether the abnormal endothelium-dependent vascular relaxation of hypertensive patients can be modified by increasing availability of nitric oxide substrate. To this purpose, 14 hypertensive patients (age 48 +/- 7 years; 9 men and 5 women) were studied with intra-arterial infusion of acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle vasodilator) before and after the infusion of L-Arginine, the natural substrate for production of endothelium-derived nitric oxide. The results were compared with those obtained in a control group of 12 normal volunteers (age 49 +/- 7 years; 7 men and 5 women) matched to the patients for age and sex. As shown previously, the vasodilator response to acetylcholine was blunted in hypertensive patients compared to controls; however, no difference was observed in the response to sodium nitroprusside. The infusion of L-Arginine did not produce any significant change in basal blood flow in either hypertensive patients or normal controls. In contrast to normal controls, the infusion of L- Arginine did not modify the vasodilator response to acetylcholine. Similarly, the response to sodium nitroprusside was not altered by L- Arginine. These findings indicate that the abnormal endothelium- dependent vasodilation of hypertensive patients is not due to decreased nitric oxide substrate availability, and further suggest a defect in the synthesis or release of nitric oxide by endothelial cells.
