ROLE OF EXTRACELLULAR CA-TYPE AND NON-L-TYPE CA++ CHANNELS IN THROMBOXANE-A(2)-RECEPTOR MEDIATED CONTRACTION IN RAT AORTA(+ INFLUX VIA L)

The purpose of this study was to investigate the role of extracellular Ca++ influx via L-type and non-L-type Ca++ channels in thromboxane A( 2) receptor-mediated contraction. In intact rat aorta, U46619, a selec tive thromboxane A(2) receptor agonist, induced concentration-dependen t increases in intracellular Ca++ ([Ca++](i)) and contraction (EC50 va lues of 5.5 and 6.1 nM, respectively). U46619 (10 nM) induced similar to 60 to 70% of maximal [Ca++](i) elevation and contraction. Treatment with verapamil, an L-type Ca++ channel blocker, before IO nM U46619 c hallenge, or during the plateau [Ca++](i) elevation and contraction, d ecreased these parameters by similar to 50%. Ni++, a nonselective bloc ker of cation channels, or SKF96365, a purported blocker of receptor-o perated Ca++ channels, further decreased the contraction and abolished the [Ca++](i) elevation that remained after verapamil treatment of 10 nM U46619-challenged vessels. Pretreatment with verapamil and Ni++ to prevent Ca++ influx and with cyclopiazonic acid to deplete [Ca++](i) stores also partially prevented U46619-induced contraction, whereas [C a++](i) elevation was abolished, These results suggest that thromboxan e A(2) receptor-mediated contraction of vascular smooth muscle partly depends on the influx of extracellular Ca++ via both L-type and non-L- type Ca++ channels, as well as a mechanism independent of [Ca++](i) el evation.