Effects of different cyclooxygenase inhibitors on the segmental distribution of pulmonary vascular resistance in the dog.
An increase in pulmonary vascular resistance (PVR) after cyclooxygenase inhibition (COI) is well documented in the dog, but the site of vasoconstriction to chemically distinct cyclooxygenase inhibitors is largely unknown. The purpose of the present study was to examine and compare equimolar concentrations of three chemically unrelated cyclooxygenase inhibitors, indomethacin (INDO; n = 6), meclofenamate (MECLO; n = 6) and ibuprofen (IBU; n = 5), upon the longitudinal distribution of PVR in the isolated canine lower left lung lobe perfused at constant flow with autologous blood. At successive increases in the blood concentration of each cyclooxygenase inhibitor, PVR was partitioned into upstream (arterial, Ra), middle (Rm) and downstream (venous, Rv) resistance by arterial and venous flow occlusion with capillary pressure estimated by a double flow occlusion technique. All three cyclooxygenase inhibitors produced significant pulmonary vasoconstriction with the largest increase in PVR after INDO (104 +/- 21%) and the smallest after IBU (69 +/- 10%). The PVR increase in the INDO and MECLO group was related to an elevation in both Ra (p less than 0.01) and Rv (p less than 0.01), whereas only Rv was increased by IBU (p less than 0.01). While none of the cyclooxygenase inhibitors increased Rm (p greater than 0.05), capillary pressure was increased from pretreatment levels by each cyclooxygenase inhibitor. Although each of the three chemically distinct cyclooxygenase inhibitors raised PVR, the segmental distribution of PVR and the magnitude of the capillary pressure increase varied at equimolar blood concentration.
Endrédi
J
J
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000.
el-Kashef
H A
HA
Hofman
W F
WF
Ehrhart
I C
IC
D000818:Animals; D004285:Dogs; D005260:Female; D007052:Ibuprofen / Q000097:blood / Q000494:pharmacology*; D007213:Indomethacin / Q000097:blood / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008469:Meclofenamic Acid / Q000097:blood / Q000494:pharmacology*; D011652:Pulmonary Circulation; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D008469:Meclofenamic Acid; D007052:Ibuprofen; D007213:Indomethacin