Prostanoids counterbalance the bronchoconstrictor activity of endothelin-1 in pigs.
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 x 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 NG-nitro-L-arginine methyl ester (L-NAME 5 mg x 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 x 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.
Clement
M G
MG
Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy.
Marzani
M
M
Dimori
M
M
Albertini
M
M
D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D000336:Aerosols; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin