Differential large and small vessel responses to serotonin in the dog hindlimb in vivo: role of the 5HT2 receptor.
Serotonin (5HT) constricts large arteries in vitro, an effect which seems contrary to 5HT-induced increases in blood flow observed in vivo. We used angiography to assess large artery responses, and blood flow (Q, electromagnetic flowmeter) to assess arteriolar responses to 5HT, norepinephrine (NE), and antagonists in the femoral circulation of the intact, anesthetized dog. 5HT constricted large arteries at a threshold dose of less than 10 micrograms/min, giving a 45 +/- 3% reduction of popliteal artery diameter at 100 micrograms/min (p less than 0.001). NE failed to constrict large arteries. With 100 micrograms/min 5HT, Q increased (delta Q = 108 +/- 26 ml/min; p = 0.001). NE decreased Q. Ketanserin, a 5HT and alpha 1-adrenergic antagonist, exerted a dose-dependent inhibition of 5HT-induced large artery constriction. Methysergide partially blocked the 5HT-induced large artery constriction. Ketanserin potentiated the Q response to 5HT whereas higher doses of methysergide reduced the Q response to 5HT. Neither indomethacin nor propranolol altered either response. Failure of NE to constrict large arteries in vivo and ketanserin antagonism of constriction produced by 5HT suggest the response to 5HT involves the 5HT2 receptor. No role for the 5HT2 receptor in blood flow responses is suggested. These observations may have implications for therapy of occlusive vascular disease.
Blackshear
J L
JL
Orlandi
C
C
Garnic
J D
JD
Hollenberg
N K
NK
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D004285:Dogs; D006614:Hindlimb / Q000098:blood supply; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D010880:Piperidines; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin; D011433:Propranolol; D009638:Norepinephrine; D007213:Indomethacin; D008784:Methysergide