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(Circulation. 1999;100:1400-1405.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Vasodilation to Bradykinin Is Mediated by an Ouabain-Sensitive Pathway as a Compensatory Mechanism for Impaired Nitric Oxide Availability in Essential Hypertensive Patients
From the Department of Internal Medicine, University of Pisa, Italy.
Correspondence to Dr Stefano Taddei, Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail s.taddei{at}int.med.unipi.it
Background—In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension.
Methods and Results—In 16 healthy subjects (49.5±5.8 years;
118.6±3.5/78.9±2.9 mm Hg) and 16 patients with essential
hypertension (47.9±4.8 years; 154.6±4.5/102.9±3.2 mm Hg), we
measured modifications in forearm blood flow (strain-gauge
plethysmography) during intrabrachial infusion of bradykinin (5, 15, or
50 ng/100 mL of forearm tissue per minute) in the presence of
saline, N
-monomethyl-L-arginine
(L-NMMA; used to inhibit NO synthase; 100 µg/100 mL of forearm tissue
per minute), and ouabain (to block Na+K+/ATPase
and prevent hyperpolarization; 0.7 µg/100 mL of
forearm tissue per minute). In healthy subjects, vasodilatation to
bradykinin was significantly blunted by L-NMMA and unaffected by
ouabain. In hypertensive patients, 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; 8 mg/100 mL of forearm tissue per
minute). In these patients, L-NMMA–induced inhibition of vasodilation
to bradykinin was restored, and ouabain was no longer effective. In a
final group 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 inhibited by simultaneous
ouabain infusion.
Conclusions—Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.
Key Words: endothelium-derived factors • hypertension • nitric oxide • bradykinin • ouabain • free radicals
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