| Project/Area Number |
17590468
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Ohu University (2006)
Yamagata University (2005) |
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Principal Investigator |
ISHIHATA Akira Ohu University, Pharmaceutical Sci, Professor, 薬学部, 教授 (40232326)
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| Co-Investigator(Kenkyū-buntansha) |
KATANO Yumi Yamagata Univ School of Med., Professor, 医学部, 教授 (70018696)
OHWADA Kazuo National Institute of Advanced Science and Technology, Principal Research Scientist, 主任研究員 (60101010)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | pathophysiology / hyperlipidemia / blood vessels / atherosclerosis / urotensin II / NO / 脈圧 / TGH |
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| Research Abstract |
1. We have recently segregated a new line of rabbit, named TGH, with severely high levels of plasma triglyceride and cholesterol. The aim of the present study was to investigate the progression of atherosclerosis and haemodynamic parameters in TGH rabbits. Japanese white (JW) and TGH rabbits (24-27 months old) were anaesthetized with ketamine and xylazine. Plasma concentrations of triglyceride were 63.1 ± 8.0 and 446.0 ± 35.2 mg/dL in JW and TGH rabbits, respectively. Blood pressure was measured by a catheter implanted in the femoral artery. Histological examinations were performed using haematoxylin-eosin and elastica-Masson trichrome staining to detect atherosclerotic lesions. The JW rabbits had no atherosclerotic lesions. In TGH rabbits, severe atherosclerotic lesions were observed throughout the aorta, especially in the aortic arch. Basal femoral arterial pressure was not significantly different between JW and TGH rabbits. However, the basal pulse pressure in TGH rabbits (48.3 ± 4.
… More
5 mmHg) was significantly greater than that of JW rabbits (28.0 ± 5.6 mmHg). Intravenous infusion of N^G-nitro-L-arginine methyl ester (L-NAME) increased the blood pressure of TGH and JW rabbits. There was no significant difference in the response to L-NAME between the two rabbit strains. The present study shows that severe atherosclerotic changes develop in TGH rabbits and suggests that the combined hyperlipidaemia is an important factor for promoting atherosclerosis in TGH rabbits. The greater pulse pressure in TGH rabbits may be due to the increased vascular stiffness with atherosclerosis. TGH rabbit line of heritable hypertriglyceridaemia will become a useful animal model for studies on the role of hyperlipidaemia in the progression of atherosclerosis and in many atherosclerosis-related diseases.
urotensin II can induce vascular smooth muscle contraction in rat aorta, and there was an aging-related decline in the urotensin II-induced contraction. Endothelial production of nitric oxide in response to urotensin II but not cyclooxygenase metabolites such as prostacyclin may play a role in reducing the vascular constriction especially in young aorta. The expression of urotensin II receptor decreased by aging. Less
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