We have shown that patients with essential hypertension have a reduced endothelium-dependent vascular response to bradykinin. However, the contribution of nitric oxide to endothelium-dependent vasodilation to bradykinin has not been investigated in humans. To address this tissue, we studied the response to bradykinin before and after administration of NG-monomethyl-L-arginine (L-AMMA) in 10 hypertensive patients and 12 normal controls. L-NMMA is an arginine analogue that competitively inhibits the synthesis of nitric oxide by the endothelial cells. Thus, the use of this substance permits the study of the nitric oxide system in the physiologic and pathophysiologic regulation of vascular tonnne. Drugs were infused into the brachial artery and the forearm blood flow response was measured by strain gauge plethysmography. As shown before, the vasodilator response to bradykinin was significantly depressed in hypertensive patients compared to normal controls. L-NMMA significantly blunted the response to bradykinin in normals but did not modify the response to bradykinin in hypertensive patients. Moreover, the response to bradykinin after inhibition of nitric oxide synthesis with L-NMMA was not significantly different between normal controls and hypertensive patients. Thus, the vasodilator effect of bradykinin in normal humans is at least partly mediated by the release of endothelium-derived nitric oxide. The equalization of the response to bradykinin after inhibition of nitric oxide synthesis indicates that the impaired response to bradykinin of hypertensive patients is related to a defect in the bioactivity of nitric oxide in these patients.
