Important recent advances in cardiovascular adrenergic mechanisms

RESUMO

Five sub-areas were taken into consideration: Adrenoceptor subclassification: Presently, 10 different adrenoceptor subtypes have been characterized by pharmacological and molecular biology studies: Ó1A-, Ó1B-, Ó1D-, Ó2A/D, Ó2B-, Ó2C-, ß1-, ß2-, ß3- and ß4-adrenoceptors. Intracellular signaling: the adrenoceptors are members of a large superfamily of receptors linked to guanine-nucleotide proteins (G proteins), Ó1-adrenoceptors are coupled to Gq proteins and activate phospholipases, especially phospholipase Cß, Ó2-adrenoceptors are coupled to G1 proteins and inhibit adenylyl cyclase and in some tissues regulate potassium and calcium channels. Both ß1 and ß2-adrenoceptors are preferentially coupled to adenylyl cyclase through GS proteins and ß3-adrenoceptors appear to be coupled to K+ channel through a pertussis toxin-sensitive G1 protein. ß4-Adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo desensitization. Influence of maturation and ageing: From birth to old age important changes occur in animal models as in humans at the receptor level, neurotransmitter process and catecholamine disposition. In general terms, one can say that maturation is associated with a gradual increase of adrenergic influence, while ageing is associated with a reduction in the role of the adrenergic system on the regulation of physiologic processes. Cotransmission: ATP and the neuropeptide Y are cotransmitters with noradrenaline. While noradrenaline is the main transmitter in vascular tissues, ATP has functional relevance in some vessels and neuropeptide Y is mainly a modulator of noradrenaline release; it seems that it has an increased role under pathophysiological conditions like ischemia. Role of endothelium on noradrenaline release: Many substances produced by the endotelium or acting through the endothelium are able to influence noradrenaline release from sympathetic nerve varicosities of the blood vessel wall: some of them, like bradykinin and angiotensin II, exert a facilitatory, while others like NO and endothelin have an inhibitory effect on noradrenaline release evoked electrical nerve stimulation.