2002 Fiscal Year Final Research Report Summary
EXPRESSION AND FUNCTIONAL ALTERATION OF POTASSIUM CHANNELS IN VASCULAR SMOOTH MUSCLE AND ENDOTHELIAL CELLS IN HYPERTENSION
| Project/Area Number |
13670720
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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 |
Circulatory organs internal medicine
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| Research Institution | UNIVERSITY OF THE RYUKYUS (2002)
Kyushu University (2001) |
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Principal Investigator |
OHYA Yusuke UNIVERSITY OF THE RYUKYUS, School of Medicine, Associate Professor, 医学部, 助教授 (30240964)
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| Project Period (FY) |
2001 – 2002
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| Keywords | hypertension / ion channel / endothelial cells / smooth muscle cells / vascular / potassium channels / calcium channels / angiotensin II |
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| Research Abstract |
Our progress during two years (2001-2002) are summarized as follows:
1) Decreased voltage-dependent potassium (Kv) currents in arterial smooth muscle cells from stroke-prone spontaneously hypertensive rats(SHR-SP)
Amplitudes of Kv currents were decreased in arterial muscle cells from SHR-SP, compared to those from normotensive control, Wistar Kyoto rats (WKY) by the use of patch clamp experiment. Antihypertensive treatment to SHR-SP with angiotensin II receptor blocker normalized the current alteration in part, and young rats did not have such alteration. Pharmacological evaluation showed that 4-aminopyridine sensitive potassium currents were decreased in SHR-SP. Quantitative RT-PCR showed that expression of Kv2.1 mRNA, was decreased among various Kv proteins. Results suggest that the sustained hypertension and/or stimulation of renin-angiotensin system alters the Kv channels.
2) Decreased Kv currents in endothelial cells from aorta of SHR-SP.
4-aminopyridine sensitive Kv currents were dec
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reased in endothelial cells from the aorta of SHR-SP, compared with WKY. Resting membrane potential in endothelia cells from SHR-SP was more depolarized than those from WKY. By the use of the antibodies for various Kv proteins, the staining of Kv1.5 in endothelial cells was decreased in SHR-SP. In the tension recording of the aorta, an application of 4-amynopyridine impaired the endothelium dependent relaxation, which was partially restored by a pretreatment of superoxide dismutase. Results suggest that the expression of Kv1.5 protein is decreased in hypertensive rats, which in turn decreases Kv current and depolarizes the cell. These alterations may contribute to the altered endothelial function by producing oxidative stress.
3) Intracellular angiotensin II (ang II) stimulates voltage-operated calcium currents (VOCC) in arterial smooth muscle.
Intracellular application of ang II stimulated VOCC. Blockers for either ang II type 1 receptor, G-protein, phospholipase C, or C-kinase inhibited the stimulating action of intracellular ang II. Results suggest that intracellular ang II binds to the type 1 receptor-like binding sites inside the cell, activates G-protein, phospholipase C, and protein kinase C, and enhances VOCC in arterial smooth muscle cells. Less
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Research Products
(8 results)
