Pulmonary vascular and airway responses to endothelin-1 are mediated by different mechanisms in the cat.
The role of cyclooxygenase product formation and thromboxane A2 receptor activation in the response to endothelin-1 (ET-1) was investigated and compared in the airways and in the pulmonary vascular bed of the intact-chest cat. Intravenous injections of ET-1, 0.3 nmol/kg, increased lung resistance and decreased dynamic compliance. Bronchoconstrictor responses to ET-1 were decreased significantly by a cyclooxygenase inhibitor and by a thromboxane receptor blocking agent. In the pulmonary vascular bed of the cat under constant flow conditions, ET-1 increased lobar arterial pressure in a dose-related manner, and pulmonary vasconstrictor responses to the peptide were not altered by a cyclooxygenase inhibitor or thromboxane receptor blocking agent. The cyclooxygenase inhibitor blocked responses to the prostaglandin precursor, arachidonic acid; and the thromboxane receptor blocking agent reduced responses to the thromboxane mimic, U-46619. The present data suggest that bronchoconstrictor responses to ET-1 are dependent on the release of arachidonic acid, the formation of prostaglandins, and activation of thromboxane A2 receptors whereas pulmonary vasoconstrictor responses to the peptide are mediated by a different mechanism.
Kadowitz
P J
PJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
McMahon
T J
TJ
Hood
J S
JS
Feng
C J
CJ
Minkes
R K
RK
Dyson
M C
MC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D017482:Receptors, Thromboxane; D012137:Respiratory System / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D016232:Endothelins; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D011451:Prostaglandin-Endoperoxide Synthases