Release of endothelin-like immunoreactivity in relation to neuropeptide Y and catecholamines during endotoxin shock and asphyxia in the pig.
The changes in endothelin-like immunoreactivity in plasma during various provocations in the pig were investigated and related to those of neuropeptide Y, noradrenaline and adrenaline. Release as revealed by overflow was determined in the spleen, kidney and femoral vascular bed (skeletal muscle) simultaneously by collecting local venous and arterial blood samples. Under basal conditions there was no net release of endothelin-like immunoreactivity from any region but a net removal (negative overflow) over the kidney. Endotoxin administration (20 micrograms kg-1 h-1 for 4 h) increased arterial endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity, noradrenaline and adrenaline seven-, 27-, 100- and 166-fold respectively, as well as splenic and renal vascular resistance. An increased overflow of endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity and noradrenaline, indicating local release, was observed in the spleen during endotoxin administration. The arterial plasma endothelin-like immunoreactivity during endotoxaemia correlated significantly with the splenic and renal vasoconstriction (r = 0.75 and 0.68 respectively). Chromatographic characterization revealed that the main portions of arterial plasma endothelin-like immunoreactivity collected during endotoxaemia corresponded to synthetic endothelin-1 and big endothelin. A similar uptake (50-90%) and plasma half-life (1-2 min) of exogenous endothelin-1-like immunoreactivity was observed both under control conditions and after endotoxin, suggesting that elevated plasma endothelin-like immunoreactivity after endotoxin was the result not of reduced clearance but rather of enhanced release. Asphyxia for 2 min did not increase arterial endothelin-like immunoreactivity but evoked an increased overflow of endothelin-like immunoreactivity, neuropeptide Y-like immunoreactivity and noradrenaline as well as vasoconstriction in the spleen. Capsaicin induced a release of neuropeptide Y-like immunoreactivity and noradrenaline from both the spleen and the kidney and of adrenaline from the adrenal, but no detectable overflow of endothelin-like immunoreactivity from any of the vascular regions. Renal nerve stimulation, renal artery occlusion for 30 min, haemorrhagic shock, hypotension induced by nitroprusside infusion or serotonin did not cause any detectable increase in arterial plasma levels or local overflow of endothelin-like immunoreactivity. It is concluded that plasma levels of endothelin-like immunoreactivity are increased, suggesting release in the pig in response to endotoxin administration and asphyxia. The possible involvement of endothelin as a mediator of the peripheral vasoconstrictor responses during these situations remains to be further established.
Pernow
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Hemsén
A
A
Hallén
A
A
Lundberg
J M
JM
D000818:Animals; D001237:Asphyxia / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D016232:Endothelins / Q000097:blood / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D012079:Renal Circulation / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine
D016232:Endothelins; D009478:Neuropeptide Y; D012701:Serotonin; D002211:Capsaicin; D009638:Norepinephrine; D004837:Epinephrine