Effects of endothelin-1 on arterial pressure: a comparison of intravenous and intra-arterial administration in conscious rabbits.
1. Intravenous endothelin-1 releases endothelium-derived relaxing factor (EDRF) and prostacyclin from the lungs, and substantial pulmonary clearance is claimed. Since these vaso-active substances could alter the haemodynamic effects of endothelin-1, the effects of boluses of endothelin-1 injected intravenously and into the left ventricle (intra-arterial) were compared, measuring arterial pressure and heart rate in conscious male New Zealand rabbits. The pulmonary clearance of endothelin-1-like immunoreactivity (Et-1LI) and initial plasma half-life were measured in anaesthetized rabbits during and after intravenous infusion of endothelin-1. 2. The effects of intravenous and intra-arterial routes of administration were not significantly different. Arterial pressure decreased (intravenous: 21.6, intra-arterial: 24.2 mmHg, P = 0.12, n = 10, t-test, 9 d.f.), then increased (intravenous: 21.2, intra-arterial: 16.4 mmHg, P = 0.33), while heart rate increased (intravenous: 66, intra-arterial: 53 beats/min, P = 0.09), then decreased (intravenous: 50, intra-arterial: 54 beats/min, P = 0.30). 3. Arterial and venous plasma levels of Et-1LI were not significantly different, venous levels increasing from 30 +/- 3 pg/mL (12 +/- 1 pmol/L) at 1 pmol/kg per min to 770 +/- 78 pg/mL (308 +/- 31 pmol/L) at 16 pmol/kg per min (n = 5). Mean initial plasma half-life was 0.6 min (range: 0.25-1.1 min). 4. It was concluded that there is no significant net pulmonary clearance of exogenously administered endothelin-1 in the conscious rabbit, and that any vaso-active factors released in the lungs by endothelin-1 do not have a significant effect on systemic arterial pressure.
Roberts-Thomson
P
P
Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia.
McRitchie
R J
RJ
Cain
M D
MD
Chalmers
J P
JP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016232:Endothelins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism; D008297:Male; D011817:Rabbits
D016232:Endothelins