Alpha 2-adrenoceptor modulation of catecholamine and neuropeptide Y responses during haemorrhagic hypotension in anaesthetized dogs.
The acute effects of oxymetazoline, an alpha 2-adrenoceptor agonist, and idazoxan, an alpha 2-adrenoceptor antagonist, on the release of neuropeptide Y were evaluated during haemorrhage in pentobarbital-anaesthetized dogs. Plasma concentrations of neuropeptide Y and catecholamines (adrenaline, noradrenaline, and dopamine) were determined in samples simultaneously collected from aorta, portal vein, and adrenal veins. In control dogs, adrenal catecholamine output, aortic concentrations neuropeptide Y and catecholamines markedly increased during the hypotension period. However, adrenal neuropeptide Y output decreased significantly during this period. Portal venous noradrenaline and neuropeptide Y concentrations increased significantly. In dogs treated with idazoxan, catecholamine output from the adrenals increased to an extent similar to that observed in control dogs. However, the increase in noradrenaline and neuropeptide Y in aortic or portal venous blood during haemorrhage was significantly potentiated in the presence of idazoxan. Administration of oxymetazoline abolished this increase, but did not alter adrenal catecholamine or neuropeptide Y output. The present study demonstrates that neuropeptide Y is co-released with noradrenaline from sympathetic nerve fibers during haemorrhage. Since the release of neuropeptide Y appeared to follow a similar time course to that of noradrenaline release, the present observations suggest that haemorrhagic hypotension enhances both neuropeptide Y and noradrenaline release presumably through a common releasing mechanism. These results also indicate that, in peripheral sympathetic nerves but not in the adrenal gland, neuropeptide Y release is also modulated presynaptically by the inhibitory alpha 2-adrenoceptors in conjunction with the noradrenaline release.
Briand
R
R
Faculty of Pharmacy, University of Montreal, Quebec, Canada.
Yamaguchi
N
N
Gagne
J
J
Nadeau
R
R
de Champlain
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood*; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D006470:Hemorrhage / Q000097:blood / Q000503:physiopathology*; D007022:Hypotension / Q000097:blood / Q000503:physiopathology*; D019329:Idazoxan; D009478:Neuropeptide Y / Q000097:blood*; D010109:Oxymetazoline / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D004146:Dioxanes; D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D010109:Oxymetazoline; D019329:Idazoxan