Endothelial modulation of 5-hydroxytryptamine-induced contraction in goat cerebral arteries

1. 1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10 −8−3 × 10 −5 M) caused concentration-dependent contractions, with EC 50 = 2.1 (1.9−2.5) × 10 −7 M and E max = 60 ± 2% of 50 mM KCl-induced contraction. 2. 2. Mechanical removal of endothelium significantly increased the E max (91 ± 8%) and did not change the EC 50 value of 5-HT-elicited contractions. 3. 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. 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. 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. 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.