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(Hypertension. 2008;52:314.)
© 2008 American Heart Association, Inc.

Original Articles

Tissue-Type Plasminogen Activator Release in Healthy Subjects and Hypertensive Patients

Relationship With β-Adrenergic Receptors and the Nitric Oxide Pathway

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

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

The relationship between adrenergic stimuli and NO in modulating tissue-type plasminogen activator (t-PA) release from endothelial cells was investigated in normotensive subjects and essential hypertensive patients. Sympathetic activation, a well-known stimulus for endogenous fibrinolysis, is also involved in the determination of cardiovascular risk in essential hypertension. However, the existence of cross-talk between adrenergic stimuli and NO availability in modulating t-PA release is not well established yet. We assessed the release of t-PA in the forearm microcirculation of 58 normotensive subjects (mean age: 47±9 years) and 44 essential hypertensive patients (mean age: 48±11 years) under specific intra-arterial adrenergic stimuli. Intrabrachial infusion of epinephrine (0.1 to 0.3 µg/100 mL per minute) induced greater t-PA release in normotensive subjects as compared with essential hypertensive patients (P<0.05). However, inhibition of NO synthase with N^G-monomethyl-L-arginine (100 µg/100 mL per minute) infusion blunted epinephrine-induced t-PA release in normotensive subjects (P<0.05) but not in essential hypertensive patients. In normotensive subjects, t-PA release by epinephrine was not affected by phentolamine (8 µg/100 mL per minute) coinfusion and was abolished in the presence of propanolol (10 µg/100 mL per minute). Intrabrachial isoproterenol (0.03 µg/100 mL per minute) induced a significant increase in t-PA release (P<0.01), an effect blunted by N^G-monomethyl-L-arginine (P<0.05). In essential hypertensive patients, the response to isoproterenol was impaired as compared with normotensive subjects and was unaffected by N^G-monomethyl-L-arginine coinfusion. In conclusion, the results of the present study demonstrate that adrenergic-induced t-PA release is mediated by β-adrenoreceptors via a mechanism involving the NO pathway. Our results show an impaired adrenergic-stimulated t-PA release among essential hypertensive patients, probably mediated via a reduced NO availability. This impaired fibrinolytic activity might contribute to the increased cardiovascular risk associated with hypertension.

Key Words: t-PA • receptors • adrenergic-β • NO • endothelium • hypertension • essential

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