| Project/Area Number |
16390157
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | OKYAMA UNIVERSITY |
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Principal Investigator |
KAWASAKI Hiromu Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (60125151)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSAKI Yuji Okayama University, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (90161786)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2004: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Perivascular nerves / Sympathetic nerves / CGRPergic nerves / Denervation method by Phenol / Reinnervating substance / Perivascular nerve remodeling / Nerve growth factor / Angiotensin II type 2 receptor / Phenol塗布除神経法 / In vivo除神経 / 高血圧自然発症ラット(SHR) / Angiotensin II / 神経再生物質 / 神経リモデリング |
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| Research Abstract |
The present project was designed to investigate remodeling of perivascular adrenergic nerves and calcitonin-gene related (CGRP)-containing (CGRPergic) nerves in normal and disease animal model. In mesenteric resistance arteries of spontaneously hypertensive rats (SHR), density of perivascular CGRPergic nerve innervation, CGRP mRNA levels of dorsal root ganglia and vasodilator response to CGRPergic nerve stimulation was decreased with aging, suggesting that remodeling of CGRPergic nerves develop with ageing. In contrast, function of adrenergic nerves was increased as CGRPergic nerve function decreased. Long-term treatment with antihypertensive drugs, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 2 receptor (AT2-R) antagonists but not calcium antagonists, beta-adrenoceptor antagonists and vasodilator, restored remodeling of CGRPergic nerves, indicating that angiotensin II is major factor for inducing CGRPergic nerve remodeling. To investigate substances f
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or restoration of perivascular nerve remodeling, experimental methods for inducing the perivascular nerve remodeling were developed in the rat. Under anesthesia, the superior mesenteric artery was exposed and phenol solution was topically swabbed by cotton bud. Density of perivascular adrenergic and CGRPergic nerve fibers in third branch of the mesenteric artery was observed by immunohistochemical techniques. Topical phenol treatment markedly reduced density of adrenergic nerves and more CGRPergic nerves, indicating that perivascular nerve remodeling is experimentally reproducible. Treatment with nerve growth factor (NGF), adrenomedullin or hepatic growth factor (HGF) or AT2 receptor stimulation after topical phenol application facilitated reinnervation of adrenergic and CGRPergic nerves, suggesting that perivascular nerves are reinnervated and/or regenerated by NGF-like substances. The present results of the project suggest that novel substances, which ameliorate perivascular nerve remodeling, contributes to develop new type of medicine for cardiovascular diseases. Less
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