EFFECTS OF ENDOTHELIN-1 ON ARTERIAL-PRESSURE - A COMPARISON OF INTRAVENOUS AND INTRAARTERIAL ADMINISTRATION IN CONSCIOUS RABBITS

1. Intravenous endothelin-1 releases endothelium-derived relaxing fact or (EDRF) and prostacyclin from the lungs, and substantial pulmonary c learance is claimed. Since these vaso-active substances could alter th e haemodynamic effects of endothelin-l, the effects of boluses of endo thelin-1 injected intravenously and into the left ventricle (intra-art erial) were compared, measuring arterial pressure and heart rate in co nscious male New Zealand rabbits. The pulmonary clearance of endotheli n-1-like immunoreactivity (Et-1LI) and initial plasma half-life were m easured in anaesthetized rabbits during and after intravenous infusion of endothelin-1. 2. The effects of intravenous and intra-arterial rou tes of administration were not significantly different. Arterial press ure 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-art erial: 16.4 mmHg, P = 0.33), while heart rate increased (intravenous: 66, intra-arterial: 53 beats/min, P = 0.09), then decreased (intraveno us: 50, intra-arterial: 54 beats/min, P = 0.30). 3. Arterial and venou s plasma levels of Et-1LI were not significantly different, venous lev els 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 clearan ce of exogenously administered endothelin-1 in the conscious rabbit, a nd that any vase-active factors released in the lungs by endothelin-1 do not have a significant effect on systemic arterial pressure.