| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Isao Faculty of Medicine, Gunma University, Professor, 医学部, 教授 (50008273)
TAKAYAMA Kiyoshige Faculty of Health Sciences, Gunma University, Professor, 医学部, 教授 (90134270)
SHIMIZU Hiroyuki Faculty of Medicine, Gunma University, Assistant Professor, 医学部, 講師 (20251100)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Research Abstract |
We investigated the presence of apelin and APJ transcripts and found high levels of apelin mRNA in the lung, heart, brain, ovary, intestine, and blood cells. It also presents in the adipocytes, arterial endothelial cells, gastric mucosal cells, and T cells. Apelin receptor APJ mRNA is seen in the adipocytes and arterial smooth muscle cells. The intravenous administration of apelin-12, apelin-13, and apelin-36 in the rats was found to significantly lower arterial blood pressure with no change in heart rate. Apelin-12 was more potent than apelin-13 or apelin-36 in reducing mean arterial pressure (MAP) in these rats. In contrast, apelin-9, apelin-10, and apelin-11 had no effect on MAP, suggesting that the C-terminal portion of apelin-36 with at least 12 amino acid residues may be required for its biological activity. We also examined the effects of a nitric oxide synthesis inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), on the depressor response of apelin-12 in the rats. The administration of apelin-12 induced the decrease in MAP after apelin-12 injection in the control rats. However, the administration of the same dose of apelin-12 caused almost no change in MAP in the rats pretreated with L-NAME, indicating that the action of apelin-12 was almost completely abolished in the presence of L-NAME. We also found that apelin significantly increased plasma NOx concentrations in rats. These results suggest that the depressor response of apelin may be dependent upon the release of nitric oxide.
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