Adrenergic receptors and their signal transduction mechanisms in hypertension

Abstract

Recent years have witnessed an astonishing proliferation in the number of known adrenoceptor subtypes and related signaling pathways, all of which can potentially be altered in hypertension. Although numerous reports have suggested altered adrenoceptors, guanine nucleotide binding regulatory proteins (G proteins) or effector mechanisms in hypertensive animals or patients, only few clear trends have emerged. Cardiac beta-adrenoceptor function is desensitized in various forms of hypertension but it is not clear whether alterations in signaling contribute to this desensitization in addition to the well documented decrease in beta 1-adrenoceptor numbers. Vascular alpha- and beta-adrenoceptor responsiveness are increased and decreased, respectively, in hypertensive animals and patients but the molecular site underlying these alterations has not unequivocally been established. Renal alpha 1- and alpha 2B-adrenoceptor numbers are frequently increased in genetically hypertensive rats but alpha 1-adrenoceptor-stimulated inositol phosphate formation is unchanged or decreased and alpha 2-adrenoceptor functions remain unclear. Renal beta-adrenoceptor numbers are elevated in many forms of hypertension but it is not clear whether this is accompanied by alterations in receptor function.