Author(s): Guimares S, Moura D
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Abstract The total and regional peripheral resistance and capacitance of the vascular system is regulated by the sympathetic nervous system, which influences the vasculature mainly through changes in the release of catecholamines from both the sympathetic nerve terminals and the adrenal medulla. The knowledge of the targets for noradrenaline and adrenaline, the main endogenous catecholamines mediating that influence, has recently been greatly expanded. From two types of adrenoceptors (alpha and beta), we have now nine subtypes (alpha1A, alpha1B, alpha1D, alpha2A/D, alpha2B, alpha2A/D, beta1, beta2, and beta3) and two other candidates (alpha1L and beta4), which may be conformational states of alpha1A and beta1-adrenoceptors, respectively. The vascular endothelium is now known to be more than a pure anatomical entity, which smoothly contacts the blood and forms a passive barrier against plasma lipids. Instead, the endothelium is an important organ possessing at least five different adrenoceptor subtypes (alpha2A/D, alpha2C, beta1, beta2, and beta3), which either directly or through the release of nitric oxide actively participate in the regulation of the vascular tone. The availability of transgenic models has resulted in a stepwise progression toward the identification of the role of each adrenoceptor subtype in the regulation of blood pressure and fine-tuning of blood supply to the different organs: alpha2A/D-adrenoceptors are involved in the central control of blood pressure; alpha1-(primarily) and alpha2B-adrenoceptors (secondarily) contribute to the peripheral regulation of vascular tone; and alpha2A/D- and alpha2C-adrenoceptors modulate transmitter release. The increased knowledge on the involvement of vascular adrenoceptors in many diseases like Raynaud's, scleroderma, several neurological degenerative diseases (familial amyloidotic polyneuropathy, Parkinson disease, multiple-system atrophy), some kinds of hypertension, etc., will contribute to new and better therapeutic approaches.
This article was published in Pharmacol Rev
and referenced in Journal of Molecular and Genetic Medicine