Tissue specific distribution, clearance and vascular effects of endothelin in the pig.
Endothelin-like immunoreactivity (-LI) was detected in the kidney, spleen, skeletal muscle, lung and in plasma of the pig. The highest tissue levels were found in the lung (1.5 +/- 0.07 pmol/g) and the lowest in the muscle (0.08 +/- 0.02 pmol/g). I.v. infusion of endothelin (20 pmol/kg/min for 20 min) increased plasma endothelin-LI from 18 +/- 3 to 628 +/- 109 pM and renal, splenic and femoral vascular resistance by 570, 430 and 50%, respectively. There was a close correlation between the increase in plasma endothelin-LI and the vasoconstrictor effects. During the infusion 92, 82 and 76% of arterial endothelin-LI was removed by the kidney, spleen and hindlimb, respectively, whereas there was no clearance over the lung or degradation in plasma. After the infusion, arterial endothelin-LI decreased with a half life of 77 s, while the renal and splenic vasoconstriction persisted for 60 min. Characterization by reversed phase HPLC revealed that endothelin-LI in plasma and tissue co-eluted with synthetic endothelin. It is concluded that endothelin has tissue specific distribution, clearance and vascular effects in the pig.
Pernow
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Hemsén
A
A
Lundberg
J M
JM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016232:Endothelins; D008297:Male; D008657:Metabolic Clearance Rate; D010455:Peptides / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D013552:Swine; D014018:Tissue Distribution; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D010455:Peptides