| Project/Area Number |
63570404
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
MAKINO Naoki Kyushu University, Bioclimatology and Medicine Medical Institute of Bioregulation Associated Professor, 生体防御医学研究所, 助教授 (60157170)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Satoshi Oita Medical College associated Professor, 医学部, 助教授 (50158440)
YANO Kenichi Kyushy University, Bioclimatology and Medicine Medical Institute of Bioregulatio, 生体防御医学研究所, 助手 (60230281)
HATA Tomoji Kyushu University, Bioclimatology and Medicine Medical Institute of Bioregulatio, 生体防御医学研究所, 助手 (90198739)
|
|---|
| Project Period (FY) |
1988 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
|
|---|
| Keywords | sodium-calcium ion exchange / calcium ion pump / [5-methyl-^3H] nitrendipine binding / heart sarcolemma / rat heart / cardiac hypertrophy / cardiac regression / alpha1-adrenoceptors / カテコラミン受容体 / アルファ-遮断剤 / ベ-タ-遮断剤 / 心筋肥大退縮 / 自然発症型高血圧ラット / Na^+ーCa^<2+>交換 / Ca^<2+>ポンプ / 膜リン脂質 / Na^+K^+ーATPase / 膜イオン輸送 / 心筋肥大 / カルシウム / 心筋細胞膜 |
|---|
| Research Abstract |
To examine Ca^<2+> transport activities in sarcolemmal membrane in cardiac hypertrophy caused by pressure overload, rats were subjected to aortic banding for 28, days. Heart-to-body weight ratio was increased by 46% in aortic-banded animals in comparison with the sham-operated rats. Ouabain-sensitive Na^+ -K^+ -ATPase activity in Sarcolemmal (SL) from hypertrophied hearts was not different from that in the control preparation. The initial rate of Na^+ -dependent Ca^<2+> - uptake in SL vesicles from the hypertrophied hearts was stimulated by 53% compared with the control vesicles. ATP-dependent Ca^<2+> uptake and Ca^<2+> -stimulated adenosinetriphosphatase (ATPase) activities in SL from hypertrophied hearts were increased by 35%. The number of Ca^<2+> channels estimated by [5-methyl-^3H] nitrendipine binding was decreased by 33% in SL from hypertrophied hearts. Total and individual phospholipid contents in the hypertrophied heart preparations were not different from those in the control
… More
, except that phosphatidylcholine and phosphatidylethanolamine contents were significantly increased. Sarcolemmal preparations from hypertrophied hearts from the 22-wk-old spontaneously hypertensive rats exhibited changes in Na^+-Ca^<2+> exchange and Ca^<2+> pump activities (similar to those observed in banded hearts), whereas the Na^+ -K^+ -ATPase activity decreased, [^3H] nitrendipine binding increased,and phospholipid contents were not different.
Additionaly, we have studied on cardiac regression of hypertrophy in these experimental animals which were induced by administration of angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) for 6 weeks. The left ventricular muscle mass and systolic pressure were decreased upon treating the hypertrophied rats with enalapril, This drug also decreased the number of alphal1-adrenocepters in hypertrophied myocardium without any changes in beta-adrenoceptors. On the other hand, treatment of the hypertrophied animals with alphal-adrenergic blocker (bunazosin, 5 mg/kg/day) or beta-adrenerg
ic blocker (propranolol, 25 mg/kg/day) for 6 weeks decreased the left ventricular mass and systolic pressure without any changes in alpha1- or beta-adrenergic receptors. The regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril for 10 weeks was also not associated with any alterations in alpha1- or beta-adrenergicreceptors in hypertrophied myocardium.
Thus, although differences were defined between two types of hypertrophy, these results suggest alterations in the sarcolemmal Ca^<2+> transport activities that may serve as an adaptive mechanism for the removal of Ca^<2+>from the myocardial cells during the development of cardiac hypertrophy. On the other hand, from results of the study in cardiac regression, regression of cardiac hypertrophy is not always associated with a decrease in the number of alpha1-adrenergic receptors and that the beneficial effects of enalapril in the hypertrophied heart in aortic banded animals may be of some specific nature. Less
|
