Contractile responses of intrapulmonary vessels from three species to arachidonic acid and an epoxymethano analog of PGH2

The contractile effects of arachidonic acid (AA) and an epoxymethano analog, chemically similar to PGH2, were investigated in helical strips of intrapulmonary artery (IPA) and vein (IPV) isolated from bovine, rabbit, and canine lung. The analog increased isometric force in a concentration-related manner in IPV from the three species and in IPA from bovine and rabbit lung over the concentration range from 10−12 to 10−6 M. Concentration of the analog up to 10−7 M had no significant contractile effects in canine IPA, although the same vascular strips responded well to a depolarizing potassium solution both before and after exposure to the analog. Of IPA and IPV from the three species, only rabbit IPA contracted in response to 10−5 M AA. Contractions of rabbit IPA induced by 10−8–10−5 M AA were blocked by 10−6 M indomethacin, a cyclooxygenase inhibitor. In contrast, AA elicited concentration-related relaxation in canine IPA partially contracted by phenylephrine. AA had no consistent effect in partially contracted canine and rabbit IPV. These results demonstrate that the epoxymethano analog exerted potent contractile effects in IPA and IPV, except in canine IPA. Since the analog is chemically similar to PGH2 and has been shown to mimic the endoperoxides or possibly TXA2, the results suggest that these intermediates may be highly potent stimulants of IPA and IPV contraction. However, the precursor of endoperoxides and thromboxanes, AA, induced significant contractile activity only in rabbit IPA. These results suggest that local production of active intermediates in IPA and IPV is low, or that the intermediates formed are broken down so rapidly that contractile effects do not occur except possibly in rabbit IPA.