Prostanoids counterbalance the bronchoconstrictor activity of endothelin-1 in pigs

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 58; no. 3; pp. 177 - 183
• Main Authors: Clement, M.G., Marzani, M., Dimori, M., Albertini, M.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.03.1998; Elsevier
• Subjects: Administration, Inhalation; Aerosols; Air breathing; Airway Resistance - drug effects; Animals; Biological and medical sciences; Blood Pressure - drug effects; Bronchoconstriction - drug effects; Cardiac Output - drug effects; Cyclooxygenase Inhibitors - pharmacology; Endothelin-1 - administration & dosage; Endothelin-1 - pharmacology; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Indomethacin - pharmacology; Lung Compliance - drug effects; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - metabolism; Prostaglandins - physiology; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Swine; Vascular Resistance - drug effects; Vertebrates: respiratory system; Peptides; Endothelin 1; Bronchomotricity; Biological activity; Pig; Vertebrata; Bronchoconstriction; Mammalia; Lung function; Nitric oxide; Prostanoid; Vasoconstrictor agent; Artiodactyla; Hemodynamics; Ungulata
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/S0952-3278(98)90111-9

In 12 anaesthetized spontaneously breathing pigs divided into two groups of six animals we evaluated the respiratory and haemodynamic responses to endothelin-1 (ET-1) administered by aerosol (200 pmol.kg −1 in 1 ml of saline solution). In the first group (control group), the responses to ET-1 were evaluated before and after the blocking of endogenous nitric oxide (NO) by N G-nitro-L-arginine methyl ester (L-NAME 5 mg.kg −1, i.v.). In the second group (indomethacin-pretreated group), the experimental protocol was similar to that of the control group, but the responses were evaluated after the blocking of endogenous prostanoids by indomethacin (3 mg.kg −1, i.v.). Results show that in the control group ET-1 administered before and after L-NAME did not change compliance (Crs) or resistances (Rrs) of the respiratory system. In indomethacin-pretreated pigs, ET-1 significantly increased Rrs and decreased Crs. This constrictor effect appearing only during the block of arachidonic acid metabolites showed that ET-1 activity can be counterbalanced by a release of dilator prostanoids. In this group after L-NAME pretreatment ET-1 did not alter the mechanical properties of the respiratory system, suggesting an involvement of other bronchodilator mechanisms. In the control group, aerosol administered ET-1 increased mean systemic (MAP) and pulmonary (MPAP) arterial pressures, while when ET-1 was administered after L-NAME pretreatment, MPAP decreased. In the indomethacin-pretreated group, the peptide did not modify MAP, but caused an early decrease in MPAP when administered after L-NAME. Therefore, our results show that ET-1 caused a bronchoconstrictor effect only in indomethacin-pretreated pigs and suggest that the intrinsic constrictor activity of the peptide can be modulated especially by the release of dilator prostanoids.