Pre- and postsynaptic adrenergic dysfunctions in hypertension.

Numerous experimental and clinical studies, using various approaches to evaluate the release of sympathetic transmitters and to obtain sympathetic nerve microneurographic recordings, have shown clearly that sympathetic system activity and reactivity is increased in experimental models of hypertension [deoxycorticosterone acetate (DOCA) salt and spontaneously hypertensive rats (SHR)] and in an important subgroup of essential hypertensive patients. This finding may reflect dysfunctions in the baroreflex blood pressure regulation, since an elevated blood pressure should normally inhibit sympathetic activity. This abnormality may arise from a variety of dysfunctions occurring at various sites along the baroreflex arc, including presynaptic modulatory adrenergic autoreceptors, where reduced sensitivity of presynaptic alpha 2 inhibitory receptors and enhanced sensitivity of beta 2 presynaptic receptors have been demonstrated. Although it has been possible to correlate the blood pressure elevation with various indices of sympathetic activity in experimental and human hypertension, the functional implications of that abnormality can be fully understood only in the light of concomitant alterations occurring in postsynaptic mechanisms. Pharmacologic, physiologic and biochemical studies strongly suggest that postsynaptic alpha 1 adrenergic functions become dominant while beta adrenergic functions are attenuated in hypertension. In experimental hypertension, this phenomenon is associated with a reduction in the number of beta adrenoceptors and in the production of its second messenger, cyclic AMP, whereas the number of alpha 1 adrenoceptors remained unchanged or increased, but the production of their second messengers, inositol triphosphate and diacylglycerol, is enhanced in cardiac and vascular tissues. These observations suggest the presence of an imbalance in postsynaptic adrenoceptor functions, which promotes the pressor effects of the sympathetic system.(ABSTRACT TRUNCATED AT 250 WORDS)