Sympathetic Abnormalities in Human Hypertension

Abstract

Elevated supine catecholamine (CA) or norepinephrine (NE) levels were reported in the blood of an important proportion of patients suffering from labile or sustained hypertension, by several groups of investigators. More recent studies have uncovered the existence of a subgroup of patients with labile hypertension characterized by elevated epinephrine (E) levels. These findings suggest an increased sympatho-adrenal tone in subgroups of hypertensive patients. Elevated circulating NE and E levels appear to reflect distinct autonomic dysfunctions since there was little overlap between patients presenting elevated levels of either of these amines. Elevated supine E levels were observed mainly in labile hypertensive patients while elevated NE levels were observed in both labile and sustained hypertensive patients. While patients with elevated supine NE levels tended to respond to postural changes by a greater elevation of NE levels, those with elevated supine E levels were characterized by a normal NE response to standing. These differences seem to be of physiological significance since supine and standing circulating responses could be correlated with the heart rate or with the myocardial contractility. Although these studies suggest a variety of sympathetic dysfunctions affecting the basal tone and the reactivity of either the sympathetic fibers or the adrenal medulla in human hypertension, these abnormalities could be the reflection of various pathological mechanisms. Beside reflecting primary dysfunctions occurring along the sympathetic reflex arc, circulating catecholamine (CA) levels could also reflect dysfunctions occurring outside the sympathetic system through an action on presynapti c modul atory mechanisms.

Among these, a close functional interraction mediated through presynaptic muscari ni c receptors has been demonstrated between the sympathetic and parasympathetic components of the autonomic nervous system and it is thus possible that a parasympathetic dysfunction could after the sympathetic tone and reactivity. Concordant with this hypothesis, the treatment with atropine was found to potentiate the increase i n circulating NE and E levels upon standing i n hypertensive patients characterized by a normal NE response to postural changes while the same treatment did not potentiate the NE postural response in patients characterized by an enhanced NE response before the treatment thus suggesting a decreased parasympathetic inhibition on the sympathetic fibers in this latter group o f patients. It thus appears that the sympathetic hyperreactivity observed in a subgroup of hypertensive patients might be secondary to a decreased inhibitory parasympatheti c tone on sympathetic fibers.