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 Emax = 60 +/- 2% of 50 mM KCl-induced contraction. 2. Mechanical removal of endothelium significantly increased the Emax (91 +/- 8%) and did not change the EC50 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 (Emax = 77 +/- 4%). 4. Incubation of unrubbed arteries with the competitive inhibitor of the NO synthesis, NG-nitro-L-arginine (L-NOARG) (10(-5) M), significantly enhanced the arterial response to 5-HT (Emax = 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 Emax 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.
Miranda
F J
FJ
Centro de Investigación, Hospital Universitario, La Fe, Valencia, Spain.
Torregrosa
G
G
Salom
J B
JB
Alabadí
J A
JA
Jover
T
T
Barberá
M D
MD
Alborch
E
E
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006041:Goats; D006072:Gossypol / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D012701:Serotonin / Q000494:pharmacology*
D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D011464:Epoprostenol; D006072:Gossypol; D007213:Indomethacin