ABSTRACT
The central neuronal systems associated with cardiovascular regulation in haemorrhagic shock can be functionally divided into two groups. The first one includes opioid peptides, which inhibit the activity of cardiovascular centre neurones and initiate the sympathoinhibitory phase of regulation in hypovolaemia. The second group consists of non-opioid systems demonstrating anti-shock properties, such as the melanocortinergic. cholecystokininergic, thyreoliberinergic, cholinergic and histaminergic systems. In the present paper, we review recent data concerning the role of the melanocortins in cardiovascular regulation in haemorrhagic shock. Melanocortin peptides, proopiomelanocortin (POMC)-derived peptides which have His-Phe-Arg-Trp sequence, are secreted in large amounts in the sympathoinhibitory phase of cardiovascular regulation in shock. Exogenous melanocortins. such as melanocyte-stimulating hormones (MSHs). adrenocorticotropic hormone (ACTH) and many ACTH fragments induce a long-lasting pressor effect with an increase in the survival rate in haemorrhage-shocked rats. The mechanisms of their action include centrally mediated activation of the sympathetic nervous system and the "cholinergic anti-inflammatory pathway". which leads to an increase in the peripheral resistance and suppression of the transcription nuclear factor appaB-dependent systemic inflammatory response. respectively. Moreover, acting peripherally, the melanocortins stimulate secretion of glucocorticoids, normalise the blood levels of nitric oxide and inhibit free radical generation in haemorrhagic shock. Further clinical studies are needed to confirm the usefulness of the melanocortins in the treatment of haemorrhagic shock in humans.
