Renal alpha 2-adrenoceptors, their locations and effects on sodium excretion.

Research on alpha 2-adrenoceptors has been explosive since the first functional or pharmacologic classification of these agents in 1977. While several properties of renal alpha 2-adrenoceptors have been characterized, their possible role in the pathophysiology of hypertension remains elusive. Under normal circumstances, alpha 1-adrenoceptors appear to be located postjunctionally and alpha 2-adrenoceptors are extrajunctional. However, following chronic alpha 1-adrenoceptor blockade with prazosin, the renal alpha 2-adrenoceptor density increases and they may assume the otherwise exclusive alpha 1-adrenoceptor postjunctional domain. This assumed role of alpha 2-adrenoceptors may explain the absence of natriuresis with the clinical use of prazosin and, if a similar change occurs in vascular tissue, the temporary nature of the first-dose phenomenon (orthostatic hypotension) that occurs with the use of this drug. Finally, our description of the "postsynaptic" location of the ubiquitous plasma membrane alpha 2-adrenoceptors in the original functional or pharmacologic basis of classification of alpha-adrenoceptors should now be updated. Under normal conditions, the predominant alpha 2-adrenoceptors on effector organ plasma membranes appear to be extrajunctional and do not ordinarily mediate the effects of sympathetic neuronally released norepinephrine. Postjunctional alpha 1-adrenoceptors remain postjunctional and ordinarily mediate effects of nerve-stimulated norepinephrine release.