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. British Journal of Pharmacology (2007) 150, 434–444. doi:10.1038/sj.bjp.0707119