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(Hypertension. 2007;49:878.)
© 2007 American Heart Association, Inc.

Original Articles

Nitric Oxide Modulates Tissue Plasminogen Activator Release in Normotensive Subjects and Hypertensive Patients

Chiara Giannarelli; Ferdinando De Negri; Agostino Virdis; Lorenzo Ghiadoni; Alessandro Cipriano; Armando Magagna; Stefano Taddei; Antonio Salvetti

From the Department of Internal Medicine, University of Pisa, Pisa, Italy.

Correspondence to Chiara Giannarelli, Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail c.giannarelli{at}int.med.unipi.it

We evaluated the possible role of NO in modulating tissue plasminogen activator (t-PA) release in the forearm microcirculation of normotensive subjects and hypertensive patients. Essential hypertensive patients are characterized by endothelial dysfunction because of a reduced NO availability and also show an impaired t-PA release. In healthy volunteers and essential hypertensive patients, we studied local t-PA release and forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.45 and 1.5 µg/100 mL/min) and of sodium nitroprusside (0.5 and 1.0 µg/100 mL/min), an endothelium-dependent and -independent agonist, respectively. Acetylcholine was also repeated in the presence of intra-arterial infusion of the NO synthase inhibitor N^G-monomethyl-L-arginine (100 µg/100 mL/min). In normotensive subjects, vasodilation to acetylcholine was blunted by N^G-monomethyl-L-arginine. In these subjects, acetylcholine infusion induced a significant, dose-dependent increase in net forearm t-PA release. N^G-monomethyl-L-arginine significantly reduced basal t-PA release, as well as acetylcholine-induced t-PA release. In essential hypertensive patients, vasodilation to acetylcholine was reduced as compared with controls and resistant to N^G-monomethyl-L-arginine. In contrast to what was observed in healthy control subjects, in hypertensive patients, acetylcholine had no effect on t-PA release. Similarly, N^G-monomethyl-L-arginine failed to modify either the tonic or the agonist-induced t-PA release. Both tonic and agonist-induced release of NO are directly involved in t-PA release by endothelial cells. Essential hypertension, characterized by a reduction in tonic and stimulated NO availability, is also associated with impaired capacity of t-PA release, suggesting a major role of impaired NO availability in worsening both vasodilation and t-PA release.

Key Words: endothelium • tissue plasminogen activator • nitric oxide • acetylcholine • microcirculation • hypertension • essential

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