ATP MODIFICATION OF SEROTONIN-INDUCED CONTRACTION OF THE RAT PULMONARY-ARTERY

Serotonin (5HT) and ATP are simultaneously released from activated pla telets at the site of vascular injury and are hypothesized to play a s ignificant role in hemostasis. Our laboratory investigated the modulat ion of vascular contraction of arterial ring segments by 5HT plus ATP as a model of the potential regulation of localized vascular tone by p latelet releasates in regions of arterial damage. This study expands o ur focus on how these two vasoactive components, released from platele t dense granules, regulate vascular tone. 5HT- and 5HT analog-induced vasoconstrictions were measured in the presence or absence of ATP and ATP analogs with intact or deendothelialized rat pulmonary arterial ri ng segments suspended in organ baths. The possible prensence of 5HT(2) and 5HT(1A) receptor types in the rat pulmonary artery was demonstrat ed by vasoconstrictions induced by 5HT and (+)-8-hydroxy-2-(di-N-propy lamino) tetralin hydrobromide (DPAT). The DPAT response was only 30%-5 0% of that induced by comparable concentrations of 5HT. The 5HT-induce d contraction was inhibited by the 5HT(2) antagonist, ketanserin. ATP equally relaxed 5HT and DPAT contracted tissue while the P-2X agonist, alpha beta-methylene ATP, increased the contracted state of DPAT-trea ted arteries to a significantly greater extent than observed with 5HT. The P-2y agonist, 3'-O-(4-benzoyl)benzoyl ATP (BzATP), the P-2X agoni st beta gamma-methylene ATP, and ATP all relaxed 5HT-induced contracti ons to similar levels under a number of physiological conditions. The final revel of 5HT-induced tissue contraction was the same whether ATP was added prior to, after, or simultaneously with 5HT. ATP and the ph osphodiesterase inhibitor, theophylline, inhibited 5HT-induced vasocon striction in an additive fashion. The ATP effects were endothelium dep endent, while the inhibition by theophylline was not. The distribution of 5HT and ATP receptor types, as indicated by these and numerous oth er studies, appears to vary within different regions of the cardiovasc ular system. Extracellular ATP can synergistically enhance or inhibit 5HT-contracted blood vessels differentially at localized regions, whic h would significantly impact on localized vascular tone, and this in t urn may modulate hemostasis and thrombosis.