Bronchopulmonary and vascular effect of endothelin in the guinea-pig.
Intravenous (i.v.) injection of endothelin in the anesthetized and ventilated guinea-pig induced a dose-dependent increase in pulmonary inflation pressure. The 1 nmol/kg dose rapidly enhanced pulmonary inflation pressure, reaching a peak at 30 s, as well as produced a marked and sustained increase in mean arterial blood pressure. A maximal increase in arterial blood pressure was observed 4 min after the injection of 1 nmol/kg endothelin and remained at a plateau for 20 min. The increase in pulmonary inflation pressure induced by endothelin was significantly enhanced by treatment of the guinea-pigs with propranolol (1 mg/kg i.v.). In contrast to what was observed in untreated guinea pigs, the injection of 1 nmol/kg endothelin in propranolol-treated animals produced within 2 min an irreversible and dramatic decrease in mean arterial blood pressure with a further decline for up to 90 min. The increase in pulmonary inflation pressure induced by 0.5 nmol/kg endothelin was also potentiated significantly in propranolol-treated guinea-pigs as compared to untreated animals. Endothelin 0.5 nmol/kg caused only a transient and non-significant increase in mean arterial blood pressure in both propranolol-treated and untreated animals. Injection of endothelin (40, 120 and 400 pmol) via the pulmonary artery into isolated guinea-pig lungs evoked significant increases in pulmonary inflation pressure and perfusion pressure accompanied by the dose-dependent release of TXB2 but, in contrast, no release of histamine. The in vitro effect of endothelin on pulmonary inflation pressure and perfusion pressure was potentiated when propranolol (1 microM) was added to the perfusion medium. These results demonstrate that the bronchopulmonary effects of endothelin are, at least in part, dissociated from the vascular action of the peptide.
Touvay
C
C
Institut Henri Beaufour, Department of Immunology, Les Ulis, France.
Vilain
B
B
Pons
F
F
Chabrier
P E
PE
Mencia-Huerta
J M
JM
Braquet
P
P
D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D010976:Platelet Count; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D016232:Endothelins; D010455:Peptides; D013929:Thromboxane B2; D013928:Thromboxane A2; D011433:Propranolol