| Project/Area Number |
63570396
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Kobe University School of Medicine |
|---|
Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University School of Medicine Associate Professor, 医学部, 助教授 (40135794)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Yasuhiro Kobe University School of Medicine Assistant Professor, 医学部, 助手 (80169755)
AKITA Hozuka Kobe University School of Medicine Assistant Professor, 医学部, 助手 (60175792)
矢谷 暁人 神戸大学, 医学部附属病院, 医員
山田 充彦 神戸大学, 医学部附属病院, 医員
|
|---|
| Project Period (FY) |
1988 – 1989
|
| Project Status |
Completed (Fiscal Year 1989)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | Serotonin / Histamine / Vascular smooth muscle cell / Vascular endothelium / Low density lipoprotein / Endothelium-derived relaxing factor / Lysophosphatidylcholine / Atrial natriuretic peptide / リゾホスホリパ-ゼ / コレステロ-ル / サイクリックGMP / 動脈硬化 / ノルエピネフリン / イノシトールリン脂質代謝 / 冠動脈スパスム |
|---|
| Research Abstract |
We obtained the following results in these 2 years.
(1) Contraction and Phosphoinositides(PI) turnover were studied in atherosclerotic(AS) and control(C) rabbit aortas. Stimulation with 5-HT in AS exhibited augmented contraction and PI labeling compared with C, although NE-induced contraction and PI labeling were identical in both groups. These results indicate that 5-HT-mediated hypercontraction and signal transduction abnormality were present in atherosclerotic arteries.
(2) Effects of endothelium-derived relaxing factor(EDRF) on histamine(HA)-induced vasocsustriction and PI turnover were studied in rabbit thoracic aorta. HA exhibited contraction and [^<32>P]Pi incorporation into PI. Removal of the endothelium and methylene blue potentiate the contraction and PI labeling induced by HA. These results suggest that PI turnover and contraction in response to HA were regulated by the negative feedback EDRF.
(3) The inhibitory effects of native low density lipoprotein(LDL) and modified LDL wi
… More
th copper oxidation and phospholipase A_2(PLA_2) on endothelium-dependent relaxation(EDR) were examined in rabbit thoracic aorta. Native LDL had no effects on ACh-induced EDR, whereas PLA_2 treated LDL and oxidized LDL inhibited EDR. Furthermore, exogeneous administration of synthetic LPC had a potent inhibitory action on EDR. These results indicate that LPC is the principal substance for the inhibitory effect of oxidized LDL.
(4) Lysophospholipase activity was measured in rabbit aorta. The enzyme did not require Ca^<2+> for its activation. Cholesterol inhibited the lysophospholipase activity. These results may imply the importance of the lysophospholipase activity inhibition by cholesterol as the responsible mechanisms for the enhanced accumulation of LPC in atherosclerotic vessels.
(5) The vasodilatory response to human arterial natriuretic peptide(hANP) were compared between normal and atherosclerotic(AS) rabbit aortas. The hANP-induced relaxation and cyclic GMP formation in AS were markedly reduced. These results suggest that hANP-induced vasodilating response through membrane-bound guanylate cyclase system is impaired in AS arteries. Less
|
