Involvement of Na+-Ca2+ exchanger in cAMP-mediated relaxation in mice aorta: evaluation using transgenic mice.
OBJECTIVE
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.


METHODS
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.


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
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.
Karashima
E
E
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nishimura
J
J
Iwamoto
T
T
Hirano
K
K
Hirano
M
M
Kita
S
S
Harada
M
M
Kanaide
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005456:Fluorescent Dyes; D005470:Fluorometry; D016257:Fura-2 / Q000031:analogs & derivatives; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010647:Phenyl Ethers / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000814:Aniline Compounds; D005456:Fluorescent Dyes; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; C098106:fura-PE3; D005576:Colforsin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D012964:Sodium; D015237:Dinoprost; D000242:Cyclic AMP; D002118:Calcium; D016257:Fura-2