Apelin and vascular dysfunction in type 2 diabetes.

摘要

The apelin receptor APJ belongs to the family of seven-transmembrane domain receptors and is coupled to inhibitory G-proteins . Apelin is synthesized as a 77 amino acid pre-pro-peptide that can be cleaved into fragments of different sizes that activate APJ . Apelin peptides have been shown to affect many biological functions in mammals including the neuroendocrine, cardiovascular, and immune systems . It can act via autocrine, paracrine, endocrine, and exocrine signalling . In the cardiovascular system apelin has been shown to increase cardiac contractility when administered in pharmacological doses , The implications of this effect have been discussed recently in this journal . Exogenous apelin lowers arterial pressure in mice and rats . This effect is largely due to vasodilation as a consequence of apelin-induced activation of the endothelial nitric oxide synthase (eNOS) . However, in conscious sheep low doses of apelin induced no significant alterations in arterial pressure . At a higher dose a clear biphasic arterial pressure response was observed consisting of initial hypotension followed by hypertension , This was accompanied by reciprocal heart rate changes that were most likely baroreflex mediated . These data suggest that the vascular actions of apelin may be complex and involve effects in addition to eNOS activation depending on the apelin dose, species, and other experimental factors. Data on apelin-induced contractions in isolated human saphenous vein preparations and on apelin-induced stimulation of myosin light chain phos-phorylarion in rat and mouse vascular smooth muscle support this notion.