Specific increase in sensitivity to serotonin of the canine hindlimb collateral arterial tree via the 5-hydroxytryptamine-2 receptor.
Evidence that platelet activation contributes to ischemia associated with atherosclerosis led us to examine the response of the limb collateral arterial tree to a platelet product, serotonin. In 23 anesthetized dogs we measured arterial diameter (angiography) and blood flow (133Xe transit) before or 2 weeks after superficial femoral artery ligation (SFAL). In normal hindlimbs blood flow increased after 5-hydroxytryptamine (5-HT) and there was a modest but measurable, dose dependent narrowing of 1- to 2-mm vessels, the major stem vessels for collateral blood flow. After SFAL, identical segments of these vessels responded to serotonin more: the slope relating dose and response became steeper (P less than 0.001), the threshold dose fell significantly (P less than 0.001), and calf blood flow fell. The vasodilator response to acetylcholine was reduced sharply after SFAL, but was still demonstrable. The 5-HT-2 serotonin antagonist, ketanserin, reversed serotonin induced spasm in the region served by collaterals (P less than 0.025). Responses to norepinephrine were not potentiated. A 5-HT-2 receptor dependent sensitization of collateral arterial vessels, and blunting of the normal vasodilator response, mediates a paradoxical decrease in perfusion induced by 5-HT in regions served by the collaterals.
D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D003097:Collateral Circulation / Q000187:drug effects*; D004285:Dogs; D005263:Femoral Artery / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011985:Receptors, Serotonin; D012701:Serotonin