Tissue-Type Plasminogen Activator Release in Healthy Subjects and Hypertensive Patients Relationship With -Adrenergic Receptors and the Nitric Oxide Pathway

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 g/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-monomethyl-L-arginine (100 g/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 g/100 mL per minute) coinfusion and was abolished in the presence of propanolol (10 g/100 mL per minute). Intrabrachial isoproterenol (0.03 g/100 mL per minute) induced a significant increase in t-PA release (P 0.01), an effect blunted by N-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-monomethyl-L-arginine coinfusion. In conclusion, the results of the present study demonstrate that adrenergic-induced t-PA release is mediated by -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. (Hypertension. 2008;52:314-321.)