ABSTRACT
In essential hypertension endothelium-dependent vasodilatation is impaired because of reduced availability of nitric oxide (NO), mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilatation to bradykinin in essential hypertensive patients. In healthy subjects and essential hypertensive patients modifications in forearm blood flow (strain-gauge plethysmography) were measured during the intrabrachial infusion of bradykinin in the presence of saline, N^-monomethyl-L-arginine ( L - N M M A , to inhibit NO-synthase), and ouabain (to block N a + K + / A T P a s e and prevent hyperpolarization). In healthy subjects, the vasodilatation to bradykinin was blunted by L - N M M A and unaffected by ouabain. In essential hypertensive patients, the response to bradykinin was not modified by L - N M M A , but reduced by ouabain. When, in a further group of hypertensive patients the response to bradykinin was repeated during intrabrachial infusion of vitamin C (a scavenger for oxygen-derived free radicals), the L - N M M A - i n d u c e d inhibition of the vaso-dilatation to bradykinin was restored while ouabain was no longer effective. In a final group of normotensive controls, the vasodilatation to bradykinin which resisted to L - N M M A was inhibited further by the simultaneous infusion of ouabain. These findings suggest that the vasodilatation to bradykinin is impaired in essential hypertensive patients because the production of N O is altered by oxidative stress, and that it is mediated by an alternative pathway possibly involving endothelium-dependent hyperpolarization.
