Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients

dBackground-In essential hypertension, endothelium-dependent vasodilation i s impaired because of reduced nitric oxide (NO) availability, which is main ly caused by oxidative stress. The present study was designed to identify t he mechanism(s) responsible for NO-independent vasodilation to bradykinin i n patients with essential hypertension. Methods and Results-In 16 healthy subjects (49.5+/-5.8 years; 118.6+/-3.5/7 8.9+/-2.9 mm Hg) and 16 patients with essential hypertension (47.9+/-4.8 ye ars; 154.6+/-4.5/102.9+/-3.2 mm Hg), we measured modifications in forearm b lood now (strain-gauge plethysmography) during intrabrachial infusion of br adykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the prese nce of saline, N-omega-monomethyl-L-arginine (L-NMMA; used to inhibit NO sy nthase; 100 mu g/100 mL of forearm tissue per minute), and ouabain (to bloc k Na+K+/ATPase and prevent hyperpolarization; 0.7 mu g/100 mL of forearm ti ssue per minute). In healthy subjects, vasodilatation to bradykinin was sig nificantly blunted by L-NMMA and unaffected by ouabain. In hypertensive pat ients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9+/-3.8 years; 155.9+/-5.5/103.7+/-3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; s mg/100 mL of forearm tissue per minute). In these patients, L-NMMA-induced inhibition of vasodilation to b radykinin was restored, and ouabain was no longer effective. In a final gro up of 6 normotensive controls (45.9+/-4.1 years; 115.1+/-2.9/79.3+/-2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inh ibited by simultaneous ouabain infusion. Conclusions-Vasodilation to bradykinin is impaired in essential hypertensiv e patients because of an NO-system alteration caused by oxidative stress, a nd it is mediated by an alternative pathway, possibly involving endothelium -dependent hyperpolarization.