The significance of platelet alpha 2-adrenoceptor and sympathetic nerve activity in the hypertensive mechanism under essential hypertension--with special reference to pressor response to norepinephrine

Abstract

Although many studies have examined the metabolism of catecholamines and cardiovascular responsiveness to norepinephrine in essential and various experimental hypertension, the role of sympathetic nervous system in the pathogenesis of hypertension has not been elucidated. In this study, therefore,the role of sympathetic nerve activity related to platelet alpha 2-adrenoceptor was investigated to clarify the mechanism in which sympathetic nervous system augments the blood pressure elevation in patients with essential hypertension (EHT). Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in 27 hospitalized patients with mild to moderate EHT and 27 normotensive subjects (NT) receiving a regular diet containing 120mEq/day of sodium and 75mEq/day of potassium. In this study, mean arterial pressure (MAP) and plasma norepinephrine concentration (pNE) was significantly higher in EHT than those in NT. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yoshimbine in EHT was also significantly higher than those in NT. There was a significant positive correlation between Bmax and age in NT, but not in EHT. A significant positive correlation was observed between the pressor response to infused norepinephrine (NE-R:increments in MAP induced by i.v. infused 0.2 micrograms/kg/min of NE) and Bmax both in NT and EHT. On the other hand, no significant correlation was found between NE-R and Kd in NT and EHT. In addition, Bmax was correlated inversely with PNE in both NT and EHT. These findings suggest that down-regulation mechanism exists in platelet alpha 2-adrenoceptor number responded to PNE levels. Moreover, the increased density of alpha-adrenoceptor might have something to do with the augmented NE-R in EHT, indicating an important pathophysiological role of this receptor in the hypertensive mechanisms in EHT.