Release of neuropeptide Y upon haemorrhagic hypovolaemia in relation to vasoconstrictor effects in the pig

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Abstract
Neuropeptide Y is co-stored with noradrenaline in peripheral sympathetic nerves, but is not present in the adrenal chromaffin cells in the pig. Plasma levels of neuropeptide Y-like immunoreactivity and catecholamines were studied upon haemorrhagic shock in the anaesthetized pig. The animals were bled in two successive steps (30 and 10 ml kg-1), resulting in a reduction of the mean arterial blood pressure by 44% and 53%, respectively. Plasma levels of noradrenaline increased abruptly after the first bleeding from 1.21 +/- 0.27 to 26.5 +/- 6.3 nmol l-1. Plasma neuropeptide Y showed a progressive increase from 62 +/- 8 pmol l-1 in the basal state to 365 +/- 98 pmol l-1 at 60 min after the first bleeding. After the second bleeding plasma neuropeptide Y and noradrenaline showed a largely parallel increase and finally reached levels of 2524 +/- 580 pmol l-1 and 316 +/- 117 nmol l-1, respectively. A veno-arterial gradient of neuropeptide Y and noradrenaline indicating local release was present over the spleen after both bleeding steps. The overflow of neuropeptide Y was delayed about 15 min compared to noradrenaline after the initial bleeding. Depletion of the neuropeptide Y content after shock in the heart and skeletal muscle supported local release also from these organs. Infusions of neuropeptide Y to obtain similar plasma concentrations as during shock (nM range) caused reduction in blood flow as determined by the radionuclide-labelled microsphere technique in several organs including spleen and skeletal muscle (threshold response at 319 +/- 22 pmol l-1) but not in heart and brain. In conclusion, both neuropeptide Y and noradrenaline were markedly elevated in plasma upon haemorrhagic shock, suggesting release from sympathetic nerve terminals. Neuropeptide Y could therefore have a role as a sympathetic neurotransmitter, and during severe stress, circulating plasma levels are in the range where vasoconstriction is evoked by exogenous NPY.

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