MECHANISMS FOR ALTERED VASCULAR FUCTION IN CARDIOVASCULAR PATHOPHYSIOLOGICAL CONDITIONS : MOLECULAR INTERPRETATION OF COMPENSATORY ROLE OF HYPERPOLARIZATION-MEDIATED VASCULAR RELAXATION
| Project/Area Number |
10670628
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | AKITA UNIVERSITY |
|---|
Principal Investigator |
SAITO Takashi SCHOOL OF MEDICINE, AKITA UNIVERSITY ASSOCIATE PROFESSOR, 医学部, 助教授 (90178484)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Hitoshi SCHOOL OF MEDICINE, AKITA UNIVERSITY RESEARCHASSOCIATE, 医学部, 助手 (70301059)
KIBIRA Satoshi SCHOOL OF MEDICINE, AKITA UNIVERSITY LECTURER, 医学部, 講師 (80234334)
ABE Toyohiko SCHOOL OF MEDICINE, AKITA UNIVERSITY LECTURER, 医学部, 講師 (30231963)
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | ENDOTHELIUM-DERIVED HYPERPOLARIZING FACTOR / CARDIOVASCULAR REMODELING / CALCIUM-ACTIVATED POTASSIUM CHANNEL / カルシウム活性化カリウムチャネル / カルシウム活性化カリウムチャンネル / カルシウム・活性化カリウムチャンネル |
|---|
| Research Abstract |
Intermediate conductance Ca-activated K channel (ImK) was cloned from cDNA library of vascular smooth muscle cells in rat pulmonary arteries (submitted to GenBank : accession No. : AF149250). Coding region of Rat ImK has 1278 base pairs, and translated protein comprises 425 amine acids forming 6 transmembrane spanning domain. Expression of ImK mRNA checked by Northern blot was ubiquitous, those include brain, heart, kidney, lung, testis, skin and also non-excitable cells. Transfected and reconstructed ImK channel carries outward K current with elevation of intracellular Ca and causes membrane hyperpolarization.
We tested differential expression of Ca-activated K channels (KCa) in postischemic rat heart. ImK showed marked increase in its expression. In situ hybridization of ImK mRNA and immunostaining of ImK protein revealed that this was not only the result of the increase in ImK expression in vascular cells but also in infiltrative leukocytes and fibroblasts. ImK gene has tyrosine phosphorylation consensus site in the proximal portion of C-terminus. These findings suggest that the increased expression of ImK is related to both inflammatory and cell-proliferative process in postischemic cardiovascular remodeling. To explore the role of AT1 receptor activation in altered expression of ImK, effect of AT1 blockade with candesartan (CAN) was tested. CAN was administered with osmotic minipump (3mg/kg/day). CAN markedly inhibited both peaks. These findings suggest that the mechanisms of the increased expression of ImK is AT1-dependent.
|
Report
(4 results)
Research Products
(15 results)
