| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Nicotine has been shown to, in the rat mesenteric artery, cause a concentration-dependent and endothelium-independent vasodilator response, which is mediated by capsaicin-sensitive nerves and is associated with the intact adrenergic nerves. In the present study, mechanisms underlying the nicotine-induced vasodilation where further investigated in mesenteric resistance blood vessels of the Wistar rat. Isolated mesenteric vascular beds without endothelium were perfused with Krebs solution and contracted by 2-5 μM methoxamine and perfusion pressure was measured with a pressure transducer.
Perfusion of nicotine (1 to 100 μM) for 1 min caused a concentration-dependent vasodilation. The nicotine-induced vasodilation was inhibited by the vanilloid receptor antagonists, capsazepine(1 to 10 μM) and ruthenium red (1 to 30 μM), but did not by DOPA receptor antagonist (L-DOPA CHE), dopamine D1 and D2 receptor antagonist (SCH 23390 and haloperidol), ATP P2X receptor desensitizing agent (α, β-methylene ATP), neuropeptide Y1 receptor antagonist (BIBP3226), and adenosine A2 receptor antagonist (8-SPT). Catecholamine metabolites including normetanephrine and 3-methoxytyramine but not homovanillic acid induced concentration dependent-vasodilation, which was not inhibited by capsaicin treatment. The proton pump inhibitor, omeprazol, inhibited the nicotine-induced vasodilation in a concentration-dependent manner. These results suggest that vanilloid receptors on CGRPergic nerves may be activated by proton released by nicotine to cause vasodilation in the mesenteric resistance artery of the rat.
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