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, Mayumi Hirano, S. Kita, M. Harada, H. Kanaide

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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 1 2007

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Sodium-Calcium Exchanger
Colforsin
Transgenic Mice
Aorta
Thoracic Aorta
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxanes
Vascular Smooth Muscle
varespladib methyl
Smooth Muscle Myocytes
Smooth Muscle
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Involvement of Na +-Ca 2+ exchanger in cAMP-mediated relaxation in mice aorta : Evaluation using transgenic mice. / Karashima, E.; Nishimura, J.; Iwamoto, T.; Hirano, K.; Hirano, Mayumi; Kita, S.; Harada, M.; Kanaide, H.

In: British Journal of Pharmacology, Vol. 150, No. 4, 01.02.2007, p. 434-444.

Research output: Contribution to journalArticle

Karashima, E. ; Nishimura, J. ; Iwamoto, T. ; Hirano, K. ; Hirano, Mayumi ; Kita, S. ; Harada, M. ; Kanaide, H. / Involvement of Na +-Ca 2+ exchanger in cAMP-mediated relaxation in mice aorta : Evaluation using transgenic mice. In: British Journal of Pharmacology. 2007 ; Vol. 150, No. 4. pp. 434-444.
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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.",
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T1 - Involvement of Na +-Ca 2+ exchanger in cAMP-mediated relaxation in mice aorta

T2 - Evaluation using transgenic mice

AU - Karashima, E.

AU - Nishimura, J.

AU - Iwamoto, T.

AU - Hirano, K.

AU - Hirano, Mayumi

AU - Kita, S.

AU - Harada, M.

AU - Kanaide, H.

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AB - 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.

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