Vascular responses to arachidonic acid in the perfused canine lung.
We compared the effects of arachidonic acid (AA), the bisenoic prostaglandin precursor, with those of prostaglandin F2a (PGF2a) and norepinephrine (NE) on pulmonary vascular resistance in the isolated (in situ), perfused canine lung lobe. The isolated lobe was perfused with autologous blood or an artificial perfusate under conditions of constant flow. Lobar artery and venous pressures were constantly monitored after bolus injections of AA, PGF2a, and NE into the inflow cannula. AA (100 mug/kg produced a significant increase in the pressure gradient (93.3 +/- 8.4%, SE) in the lobe. Similarly, PGF2a (1 mug/kg) significantly increased the pressure gradient (41.2 +/- 6.5%), as did NE (1 mug/kg, 41.6 +/- 3.2%). Aspirin (25 mg/kg) completely blocked the pulmonary vascular effect of AA, but did not affect the response to PGF2a, Linoleic acid, a control fatty acid, did not produce pulmonary vasoconstriction. The pressor effect of AA was not blocked by pretreatment with phentolamine, propranolol, cyproheptadine, or atropine. The use of an artificial perfusate free of cellular elements did not prevent the vasoconstrictor action of AA. The times to onset of action of the three agents were similar, and short. These results suggest that AA is converted into vasoactive intermediates or a prostaglandin, and the vasoactive intermediates or the prostaglandin act directly on precapillary pulmonary vascular smooth muscle rather than through platelet, plasma, adrenergic, or cholinergic mechanisms.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003533:Cyproheptadine / Q000494:pharmacology; D004285:Dogs; D008041:Linoleic Acids / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*
D001095:Arachidonic Acids; D008041:Linoleic Acids; D011460:Prostaglandins F; D003533:Cyproheptadine; D001285:Atropine; D011433:Propranolol; D001241:Aspirin; D009638:Norepinephrine; D010646:Phentolamine