Abstract:
:The bronchopulmonary and pressor effects of endothelin-1 (ET-1), a newly described vasoconstrictor peptide produced by endothelial cells, were investigated in the guinea pig. Intravenous injection of ET-1 (1 nmol/kg) induced an increase in pulmonary inflation pressure (PIP) as well as an important and sustained increase in arterial blood pressure (BP). Pretreatment of these animals with propranolol (1 mg/kg i.v.), provoked a significant enhancement of the ET-1-induced increase in PIP, accompanied by a dramatic and significant decrease of BP. When administered by aerosol for 1 min, ET-1 (1, 5, or 10 micrograms/ml) induced a dose-dependent increase in PIP that was maximal by 4-5 min, but no significant change of BP. Pretreatment of guinea pigs with propranolol (1 mg/kg), mepyramine (1 mg/kg i.v.), nifedipine (50 mg/kg i.p.), or verapamil (0.3 mg/kg i.v.) did not inhibit the bronchopulmonary response evoked by aerosol administration of 10 micrograms/ml of ET-1. In contrast, pretreatment of the animals with indomethacin (10 mg/kg i.v.) or BN 52021 (10 mg/kg i.v.) significantly reduced the bronchopulmonary response of ET-1 given by aerosol. Injection of ET-1 (0.1, 0.3, and 1 micrograms) into isolated guinea pig lungs caused significant increases in PIP that were accompanied by the release of TxB2 but not histamine. These results demonstrate that ET-1 induces bronchopulmonary alterations in the guinea pig that appear to be dissociated from the systemic vascular effects of the peptide.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Braquet P,Touvay C,Lagente V,Vilain B,Pons F,Hosford D,Chabrier PE,Mencia-Huerta JMdoi
10.1097/00005344-198900135-00036subject
Has Abstractpub_date
1989-01-01 00:00:00pages
S143-6; discussion S150eissn
0160-2446issn
1533-4023journal_volume
13 Suppl 5pub_type
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