Analysis of responses to pentoxifylline in the pulmonary vascular bed of the cat.
OBJECTIVE
To test the hypothesis that pulmonary vasodilator responses to pentoxifylline are dependent on the synthesis of nitric oxide from L-arginine and are independent of the release of cyclooxygenase products.


METHODS
Prospective study.


METHODS
Research laboratory.


METHODS
Isolated lobar lung preparation, using mongrel cats.


METHODS
In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, and the effects of a cyclooxygenase blocker, meclofenamate, were investigated on pulmonary arterial responses to pentoxifylline, acetylcholine, and isoproterenol during increased tone conditions induced by the thromboxane A2 mimic, U46619, in the pulmonary vascular bed of the cat.


RESULTS
Lobar arterial perfusion pressure, systemic pressure, and left atrial pressure were continuously monitored, electronically averaged, and permanently recorded. Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, NG-L-nitro-L-arginine methyl ester significantly reduced the vasodilator responses to pentoxifylline and to acetylcholine, whereas NG-L-nitro-L-arginine methyl ester had no significant effect on the vasodilator responses to isoproterenol. Vasodilator responses to pentoxifylline and acetylcholine were not significantly changed in the presence of meclofenamate, whereas meclofenamate markedly reduced the vasopressor effects of arachidonic acid.


CONCLUSIONS
These data show that pentoxifylline has significant vasodilator activity in the pulmonary vascular bed of the cat. The present data also suggest that responses to pentoxifylline during increased tone conditions may, in part, be mediated by the release of nitric oxide and are independent of the release of cyclooxygenase products.
Kaye
A D
AD
Department of Anesthesiology, Tulane University Medical School, New Orleans, LA, USA.
Ibrahim
I N
IN
Kadowitz
P J
PJ
Nossaman
B D
BD
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010431:Pentoxifylline / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001993:Bronchodilator Agents; D016861:Cyclooxygenase Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D007545:Isoproterenol; D000109:Acetylcholine; D010431:Pentoxifylline; D019331:NG-Nitroarginine Methyl Ester