2000 Fiscal Year Final Research Report Summary
Pathophysiological roles for cardiac steroid hormone biosynthesis
| Project/Area Number |
11838003
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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 Institution | Kanazawa University |
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Principal Investigator |
TAKEDA Yoshiyu Kanazawa University, School of Medicine, Associate professor, 医学部, 助教授 (90242544)
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| Project Period (FY) |
1999 – 2000
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| Keywords | cardiomyocyte / messenger RNA / aldosterone synthase / aldosterone / cardiac hypertrophy |
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| Research Abstract |
Aldosterone is synthesized in extra-adrenal tissues ; both blood vessels and brain. We undertook this study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, angiotensin-converting enzyme (ACE) inhibition, and angiotensin II on aldosterone *nthesis in the heart. To clarify the pathophysiologic role of cardiac aldosterone in the hypertentsive heart, we compared the synthesis of aldosterone in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) with those in Wistar-Kyoto rats. The effects of the aldosterone antagonist spironolactone on myocardial hypertrophy in adrenalectomized SHRSP were also studied. Isolated rat hearts were perfused for 2 hr, and the perfusate analyzed by high-performance liquid chromatography and mass spectrometry. The activity of aldosterone synthase was estimated by the conversion of [^<14>C] deoxycorticosterone to [^<14>C] aldosterone. The levels of aldosterone synthase gene (CYP11B2) mRNA were determined by competitive polymerase chain reaction. Aldosterone production, the activity of aldosterone synthase, and the expression of CYP11B2 mRNA were increased in hearts from adrenalectomized rats and rats treated with angiotensin II.ACE inhibitors decreased cardiac aldosterone synthesis. Cardiac aldosterone, aldosterone synthase activity and CYP11B2 mRNA levels in hearts from 2- and 4-week-old SHRSP were significantly greater than those of age-matched WKY rats. Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP.These results suggest that the rat heart produces aldosterone and endogenous cardiac aldosterone may affect cardiac function and hypertrophy in hypertension in rats.
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Research Products
(6 results)
