Pharmacological modulation of the bronchopulmonary action of the vasoactive peptide, endothelin, administered by aerosol in the guinea-pig.
Administration by aerosol for 1 min of solutions of endothelin (ENDO; 1, 5 or 10 micrograms/ml) to anaesthetized and ventilated guinea-pigs induced a dose-dependent bronchopulmonary response (BR) which was maximal within 4 to 5 min. In contrast, no significant change of the mean arterial blood pressure was observed. Pretreatment of guinea-pigs with propranolol (1 mg/kg, i.v.), mepyramine (1 mg/kg, i.v.), nifedipine (50 mg/kg, i.p.) or verapamil (0.3 mg/kg, i.v.) did not significantly affect the BR induced by an aerosol of a solution of 10 micrograms/ml ENDO. In contrast, BR was significantly reduced when the animals were pretreated with the cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.v.) or the platelet-activating factor (PAF) receptor antagonist, BN 52021 (10 mg/kg, i.v.). These results indicate that aerosolized ENDO induces a BR via the generation of secondary mediators such as cyclooxygenase products and PAF in a process which is unaffected by the blockers of the voltage-dependent calcium channels.
Lagente
V
V
Institut Henri Beaufour, Les Ulis, France.
Chabrier
P E
PE
Mencia-Huerta
J M
JM
Braquet
P
P
D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D004224:Diterpenes; D016232:Endothelins; D004730:Endothelium, Vascular; D046934:Ginkgolides; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000336:Aerosols; D004224:Diterpenes; D016232:Endothelins; D046934:Ginkgolides; D007783:Lactones; D010455:Peptides; D010936:Plant Extracts; D010972:Platelet Activating Factor; D011433:Propranolol; D014700:Verapamil; C045856:ginkgolide B; D011738:Pyrilamine; D009543:Nifedipine; D007213:Indomethacin