Role of intracellular Ca 2+ in endothelium-dependent contraction and relaxation of rabbit intrapulmonary arteries

Abstract

We examined whether Ca 2+ mobilizers induce endothelium-dependent contraction and relaxation (EDC and EDR) in isolated rabbit intrapulmonary arteries. Ionomycin (10 −7 M) and A-23187 (10 −7 M), both Ca 2+ ionophores, and thapsigargin (10 −6 M), an endoplasmic reticulum Ca 2+-ATPase inhibitor, caused a contraction in the non-contracted preparations, and a transient relaxation followed by a transient contraction and sustained relaxation in the precontracted preparations. Endothelium-removal abolished the contraction and transient relaxation (EDC and EDR) but not sustained relaxation (endothelium-independent relaxation, EIR). In the noncontracted preparations, ionomycin-induced EDC was significantly attenuated by quinacrine (10 −5 M), manoalide (10 −6 M), both phospholipase A 2 inhibitors, indomethacin (10 −5 M) and aspirin (10 −4 M), both COX inhibitors, and ozagrel (10 −5 M), a TXA 2 synthetase inhibitor. In the precontracted arteries, EDR was markedly reduced by L-NAME (10 −4 M), a NOS inhibitor, and methylene blue (10 −6 M), a guanylate cyclase inhibitor, and was enhanced by indomethacin, aspirin and ozagrel, probably due to inhibition of EDC. ZM230487, a 5-lipoxygenase inhibitor, had no effect on EDR. EIR was not affected by L-NAME, indomethacin or ZM230487. Arachidonic acid (10 −6 M) evoked EDC sensitive to indomethacin and ozagrel. L-Arginine (10 −3 M) caused EDR sensitive to L-NAME in the ionomycin-stimulated preparations. In conclusion, Ca 2+ mobilizers cause EDC and EDR via production of TXA 2 and NO, respectively.