5-Hydroxytryptamine dominates over thromboxane A2 in reducing collateral blood flow by activated platelets.
Intra-aortic infusion of collagen (100 micrograms/kg in 1 min) elicited an extensive platelet activation and transient but marked reductions of blood flow and increases of peripheral vascular resistance, both responses 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, + parachlorophenylalanine 100 mg/kg sc daily for 3 days), but not cyclooxygenase inhibition (indomethacin, 5 mg/kg iv) or thromboxane (Tx) A2/prostaglandin endoperoxide receptor antagonism (sulotroban, 2.5 mg/kg iv), largely prevented the collagen-induced perfusion defect without interfering substantially with the platelet activation process. TxA2 synthase inhibition, alone (dazoxiben, 5 mg/kg iv) or combined with TxA2-prostaglandin endoperoxide receptor antagonism (ridogrel, 2.5 mg/kg iv), partially reduced the collagen-induced perfusion defect and limited to a similar extent the initial platelet aggregation and release of 5-hydroxyindoles and TxB2 while increasing plasma levels of prostacyclin. These results suggest that platelet-derived 5-HT dominates over TxA2 in reducing blood flow in collateral-dependent tissue of the cat hindlimb.
Loots
W
W
Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
De Clerck
F
F
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002415:Cats; D003094:Collagen / Q000494:pharmacology; D003097:Collateral Circulation / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D015539:Platelet Activation / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000494:pharmacology*
D012701:Serotonin; D013928:Thromboxane A2; D003094:Collagen