Involvement of Na+-Ca2+ exchanger in cAMP-mediated relaxation in mice aorta: evaluation using transgenic mice.
BACKGROUND AND PURPOSE: Although vascular smooth muscle cells are known to express the Na+-Ca2+ exchanger (NCX), its functional role has remained unclear, mainly because of its relatively low expression. We thus investigated the involvement of NCX in the mechanism for the forskolin-induced vaso-relaxation, using wild type (WT) and transgenic (TG) mice that specifically over-express NCX1.3 in smooth muscle. EXPERIMENTAL APPROACH: We examined the relaxing effect of forskolin during the pre-contraction induced by 100 nM U46619, a thromboxane A2 analogue in the mouse isolated thoracic aorta. We also measured the intracellular Ca2+ concentration ([Ca2+]i) in fura-PE3-loaded aortic strips. KEY RESULTS: The forskolin-induced decreases in [Ca2+]i and tension were much greater in aortas from TG mice than in those from WT mice. In a low Na+ solution, forskolin-induced decreases in [Ca2+]i and tension were greatly inhibited in both groups of aortas. In WT aortas, the presence of 100 nM SEA0400, an NCX inhibitor, had only a little effect on the forskolin-induced decreases in [Ca2+]i, but inhibited the forskolin-induced relaxation. However, in TG aortas, the presence of SEA0400 greatly inhibited the forskolin-induced decreases in [Ca2+]i and tension. CONCLUSIONS AND IMPLICATIONS: The NCX was involved in the forskolin-induced reduction of [Ca2+]i and tension in the mouse thoracic aorta. Measurement of [Ca2+]i and tension in aortas of the TG mouse is thus considered to be a useful tool for evaluating the role of NCX in vascular tissue.