Influence of inhibitors of prostaglandin synthesis on the canine pulmonary vascular bed.
The effects of two chemically dissimilar inhibitors of prostaglandin (PG) synthesis on vascular resistance and responses to pressor and depressor hormones were evaluated in the canine pulmonary vascular bed. Indomethacin or meclofenamate, 2.5-5 mg/kg iv, increased lobar arterial pressure. Since lobar blood flow was held constant and left atrial pressure did not change, the rise in pressure reflects an increase in vascular resistance. The rise in lobar pressure after indomethacin occurred in the absence of a change in lobar venous or translobar airway pressure. This agent enhanced the response to angiotensin but not to norepinephrine. Meclofenamate decreased responses to both agents. Indomethacin enhanced the dilator response to PGE1 and both indomethacin and meclofenamate increased the response to PGF2alpha. These data indicate that the rise in resistance after indomethacin or meclofenamate was the result of vasoconstriction in vessels upstream to the small veins, presumed to be small arteries. These data are consistent with the hypothesis that under resting conditions synthesis of a dilator prostaglandin may be important for the maintenance of the pulmonary vascular bed in a dilated state. However, results of the present study are not consistent with the postulate that prostaglandins modulate responses to norepinephrine but suggest that indomethacin and meclofenamate interfere with the inactivation of PGF2alpha and PGE1 in the lung.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D062367:ortho-Aminobenzoates; D000804:Angiotensin II; D008469:Meclofenamic Acid; D009638:Norepinephrine; D007213:Indomethacin