Influence of inhibitors of prostaglandin synthesis on venoconstrictor responses to bradykinin.

The interrelationship between prostaglandins (PGs) and bradykinin (BK) was studied in isolated canine saphenous veins. The hypothesis that PGs mediate the venoconstrictor effect of bradykinin was evaluated by determining the influence of low concentrations of indomethacin (Indo) (1 muM) or eicosa-5,8,11,14-tetraynoic acid (ETA) (3 muM), two inhibitors of PG synthesis, on cumulative concentration-response curves for BK or norepinephrine (NE). In the tissue bath, responses to BK improved with time while responses to NE did not vary. When strips were least responsive to BK, Indo and ETA enhanced these responses. When strips were most responsive to BK, neither inhibitor enhanced the responses. Neither Indo nor ETA altered responses to NE. Phentolamine (10(-8) M) did not alter responses to BK. These data suggest that endogenous PGs act to attenuate, rather than mediate, the venoconstrictor response to BK. Progressive enhancement of responses to BK of untreated saphenous vein strips is associated with a decreased ability of inhibitors of PG synthesis to enhance those responses also. Thus, there may be a time-related decrease in the ability of this preparation to synthesize PGs. From the present results, it cannot be determined whether saphenous veins in vivo are highly responsive or relatively unresponsive to the peptide. However, these data do suggest that PGs are a determinant of venous responsiveness to BK.