5-HYDROXYTRYPTAMINE DOMINATES OVER THROMBOXANE-A(2) IN REDUCING COLLATERAL BLOOD-FLOW BY ACTIVATED PLATELETS

Intra-aortic infusion of collagen (100 mug/kg in 1 min) elicited an ex tensive platelet activation and transient but marked reductions of blo od flow and increases of peripheral vascular resistance, both response s being more pronounced in collaterals than in normal arterial beds in feline hind legs. Blockade of 5-hydroxytryptamine (5-HT) subtype 2 (5 -HT2) receptors for 5-HT (ketanserin or ritanserin, 0.63 mg/kg iv, -10 min) or amine depletion (reserpine, 0.1 mg/kg im, -10 days, + parachl orophenylalanine 100 mg/kg sc daily for 3 days), but not cyclooxygenas e inhibition (indomethacin, 5 mg/kg iv) or thromboxane (Tx) A2/prostag landin endoperoxide receptor antagonism (sulotroban, 2.5 mg/kg iv), la rgely prevented the collagen-induced perfusion defect without interfer ing substantially with the platelet activation process. TxA2 synthase inhibition, alone (dazoxiben, 5 mg/kg iv) or combined with TxA2-prosta glandin endoperoxide receptor antagonism (ridogrel, 2.5 mg/kg iv), par tially reduced the collagen-induced perfusion defect and limited to a similar extent the initial platelet aggregation and release of 5-hydro xyindoles and TxB2 while increasing plasma levels of prostacyclin. The se results suggest that platelet-derived 5-HT dominates over TxA2 in r educing blood flow in collateral-dependent tissue of the cat hindlimb.