Biotransformation and cardiovascular effects of arachidonic acid in the dog.
The biotransformation and cardiovascular effects of arachidonic acid (AA) were studied in the circulation of anaesthetized dogs. Arterial blood was continuously bioassayed for arachidonate metabolites using the blood-bathed organ technique of Vane. AA (5-10 microgram/ml) infused into an incubation coil of flowing blood was converted into a labile substance which contracted the vascular tissues (rabbit aorta, RbA; rabbit coeliac and mesenteric arteries, RbCA and RbMA; bovine coronary artery, BCA) and the gastrointestinal smooth muscle strips (rat stomach strip, RSS; rat colon, RC). These effects could be mimicked by exogenously generated thromboxane A2 (TXA2). Conversion of AA was inhibited by indomethacin and the selective thromboxane synthetase inhibitor, imidazole (100 microgram/ml). The half-life of TXA2 in blood was 30-47 sec, a similar value to that found in aqueous solutions at 37 degrees C. PGH2 was also converted in blood to other product(s) which contracted RSS and RC, relaxed RbCA and RbMA but had little effect on RbA. Intravenous infusion of AA (50-800 microgram kg-1 min-1) caused effects on the bioassay tissues which could be mimicked by prostacyclin. The AA infusion also induced falls in pulmonary and systemic arterial pressures and bradycardia. All effects were abolished by indomethacin (5 mg/kg) or aspirin (200 mg/kg). Radioimmunoassay confirmed that the major product of intravenously infused AA was 6-oxo-PGF1alpha, the chemical degradation product of prostacyclin. Thus, although AA is transformed to the vasoconstrictor TXA2 when incubated for sufficient time with blood alone, on rapid pulmonary transit it is transformed into a prostacyclin-like substance.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001711:Biotransformation; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011463:Prostaglandins H / Q000378:metabolism; D013928:Thromboxane A2 / Q000097:blood
D001095:Arachidonic Acids; D011463:Prostaglandins H; D013928:Thromboxane A2; D001241:Aspirin; D007213:Indomethacin