Involvement of Na +-Ca 2+ exchanger in cAMP-mediated relaxation in mice aorta: Evaluation using transgenic mice

E. Karashima, J. Nishimura, T. Iwamoto, K. Hirano, M. Hirano, S. Kita, M. Harada, H. Kanaide

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8 Citations (Scopus)

Abstract

Background and purpose: Although vascular smooth muscle cells are known to express the Na +-Ca 2+ 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 A 2 analogue in the mouse isolated thoracic aorta. We also measured the intracellular Ca 2+ concentration ([Ca 2+] i) in fura-PE3-loaded aortic strips. Key results: The forskolin-induced decreases in [Ca 2+] 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 [Ca 2+] 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 [Ca 2+] i, but inhibited the forskolin-induced relaxation. However, in TG aortas, the presence of SEA0400 greatly inhibited the forskolin-induced decreases in [Ca 2+] i and tension. Conclusions and Implications: The NCX was involved in the forskolin-induced reduction of [Ca 2+] i and tension in the mouse thoracic aorta. Measurement of [Ca 2+] 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.

Original languageEnglish
Pages (from-to)434-444
Number of pages11
JournalBritish Journal of Pharmacology
Volume150
Issue number4
DOIs
Publication statusPublished - Feb 2007

All Science Journal Classification (ASJC) codes

  • Pharmacology

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