1997 Fiscal Year Final Research Report Summary
Roles of central digitalis-like factor in stress and cardiovascular diseases
| Project/Area Number |
07457164
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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 |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
GOTO Atsuo University of Tokyo Hospital, Associate Proffessor, 医学部・付属病院, 助教授 (00150277)
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| Co-Investigator(Kenkyū-buntansha) |
NAGOSHI Hiroshi University of Tokyo Hospital, Associate, 医学部・附属病院, 医員
YAMADA Kaoru Sanraku Hospital, Dept.of Human Dry Dock, Director, 健康管理科, 科長
SHIN Wee Soo University of Tokyo Health Service Center, Director, 保健センター, 助手 (10211971)
TOYOOKA Teruhiko University of Tokyo Health Service Center, Director, 保健センター, 所長 (00146151)
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| Project Period (FY) |
1995 – 1997
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| Keywords | stress / ouabain / central nervous system / sodium / hypertension / cardiovascular diseases / risk factor / sympathetic neruous system |
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| Research Abstract |
#1 We destroyed rat central catecholamine (CA) neurons with intracerebroventricular injection of 6-hydroxydopamine and found that hypothamic ouabainlike compound (OLC) content and plasma OLC level were markedly decreased in accordance with reduced brain norepinephrin content. OLC may be closely related to central CA neurons. #2 We tested the hypothesis that OLC may participate in a homeostatic response to acute stress. Adrenal and plasma OLC levels increased in response to acute swim stress. OLC may function as a stress hormone. #3 An expansion of body fluid volume may induce the release of humoral factors, which could increase systemic vasular resistance and cause volume-dependent, forms of hupertension. Acute volume expansion could induce a similar enhanced vascular Ca2+ channel activity to that seen in hypertension, suggestin a possible contribution of circulating OLC.#4 We determined the plasma aldosterone concentration during sodium depletion in rats immunized against ouabain and
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found decreased aldosterone concentration in these rats. Endogenous OLC may play an important role in the regulation of aldosterone secretion and/or production. #5 We measured plasma and urine levels of OLC to evaluate its role in the hypertensive mechanisms in a 64-year-old male patient with ectopic adrenocorticotrophin (ACTH) syndrome due to jung cancer. The maximum plasma level was 40-fold the normal subject's range. Plasma and urine levels of OLC correlated with systolic blood pressure (BP) and diastolic BP.OLC with biological activity could account for this mineralocorticoid-type hypertension. The contribution of OLC to ACTH-induced hypertension was suggested also in rats. #6 We measured office BO,ambulatory BP (ABP) and plasma electrolytes in 82 essential hypertensive patients and found that in essential hypertensives plasma K concentration is inversely related to ABP including daytime and nighttime BOs.K may be a factor determining the whole day BP in essential hypertension. #7 We investigated the potential roles of circulating OLC in the regulation of Na and K distribution between the cells and the extracellular fluid. Consistent lower plasma K levels and steeper Na and K gradients were observed in rats immunized against ouabain. K handling in response to hypertonic NaCl load was altered and lower plasma K level was maintained in these rats. Chronic administration of PST-2238, a newly developed antiouabain agent, significantley lowered plasma K levels in rats with subtotal nephrectomy. OLC may determine the internal Na Nd K distribution and the transmembrane cation gradients in vivo. #8 We injected intraperitoneally hypertonic NaCl solution to rats and found the elevation of OLC levels in plasma, pituitary and adrenal in response to hypertonic NaCl load. OLC may play an important role in the elimination of excess body Na with hypernatremia. Less
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