ENDOTHELIAL MODULATION OF 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION IN GOAT CEREBRAL-ARTERIES

1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10(-8)-3 x 10(-5) M) caused concentration-dependent contractions, with EC50 = 2.1 (1.9-2.5) x 10(-7) M and E(max) = 60 +/- 2% of 50 mM KCl-induced contraction. 2. Mechanical removal of endothelium significantly increased the E(max) (91 +/- 8%) and did not change the EC, value of 5-HT-elicited contractions. 3. Incubation of unrubbed arteries with the irreversible inhibitor of EDRF, gossypol (10(-5) M), significantly increased the contractile response to 5-HT (E(max) = 77 +/- 4%). 4. Incubation of unrubbed arteries with the competitive inhibitor of the NO synthesis, N(G)-nitro-L-arginine (L-NOARG) (10(-5) M), significantly enhanced the arterial response to 5-HT (E(max) = 71 +/- 5%). The effects of L-NOARG were reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). 5. Pretreatment with the inhibitor of cyclooxygenase, indomethacin (10(-5) M), significantly increased the response of unrubbed arteries to 5-HT, with an E(max) of 69 +/- 3%. 6. These results suggest that endothelium modulates the constrictor effect of 5-HT in goat cerebral arteries by producing both EDRF, probably NO, and prostacyclin.