The role of cyclooxygenase in the feline pulmonary vascular bed.
OBJECTIVE
There are extensive data on roles of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2) enzymes in temperature, coagulation, and inflammatory modulation. There is little known of the function of these enzymes in regulating tone in pulmonary vasculature. The purpose of this investigation was to elucidate the roles of COX 1 and 2 enzymes in the feline pulmonary vascular bed.


METHODS
Prospective vehicle controlled study.


METHODS
University research laboratory.


METHODS
Intact chest preparation; adult mongrel cats.


METHODS
The effects of intravascular administration of U46619, angiotensin II, prostaglandin E1 (PGE1), arachidonic acid, and norepinephrine, were analyzed before and after intravascular administration of selective COX enzyme inhibitors.


RESULTS
Because lobar arterial flow is constant in these experiments, changes in lobar pressure represent changes in pulmonary arterial resistance. Under constant flow conditions, lobar arterial and systemic pressures were continuously monitored, electronically averaged, and recorded. In the isolated left lower lobe of the feline lung bed, U46619, angiotensin II, arachidonic acid, and norepinephrine induced a dose-dependent vasoconstrictor response. PGE1 induced a dose-dependent vasodepressor response. After administration of the COX 1 inhibitor SC 560, the arachidonic acid-induced vasopressor responses were significantly attenuated while U46619, angiotensin II, and norepinephrine-induced vasopressor, and PGE1-induced vasodepressor responses were not significantly altered. After administration of the COX 2 inhibitor nimesulide, both the PGE 1 vasodepressor responses and arachidonic acid-induced vasopressor responses were significantly decreased while the U46619, angiotensin II, and norepinephrine-induced vasopressor responses were not significantly attenuated.


CONCLUSIONS
The results of the study indicate that PGE1 has potent vasodepressor effects in the feline lung bed and this response is mediated by COX 2 pathways. The data also suggest that arachidonic acid has potent vasopressor activity in the feline pulmonary vascular bed and this response is mediated by both COX 1 and COX 2 sensitive pathways.
Kaye
Alan D
AD
Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. akaye@lsuhsc.edu
Hoover
Jason M
JM
Kaye
Aaron J
AJ
Ibrahim
Ikhlass N
IN
Phelps
James
J
Baluch
Amir
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002415:Cats; D051545:Cyclooxygenase 1 / Q000494:pharmacology / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000494:pharmacology / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000527:Alprostadil; D009638:Norepinephrine