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EFFECTS OF ENDOTHELIN‐1 ON ARTERIAL PRESSURE: A COMPARISON OF INTRAVENOUS AND INTRA‐ARTERIAL ADMINISTRATION IN CONSCIOUS RABBITS
Author(s) -
RobertsThomson P.,
McRitchie R. J.,
Cain M. D.,
Chalmers J. P.
Publication year - 1994
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1994.tb02521.x
Subject(s) - medicine , endothelin receptor , blood pressure , arterial blood , prostacyclin , endothelins , anesthesia , ventricle , heart rate , mean arterial pressure , hemodynamics , endothelin 3 , receptor
SUMMARY 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.