| Co-Investigator(Kenkyū-buntansha) |
KOIDE Hisashi Osaka Medical College, Assistant, 医学部, 助手 (40195649)
YAMAMOTO Shouji Osaka Medical College, Assistant, 医学部, 助手 (00148397)
NISHIMURA Hikaru Osaka Medical College, Assistant, 医学部, 助手 (40172697)
SUWA Michihiro OsaKa Medical College, Assistant, 医学部, 助手 (00140145)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Research Abstract |
Basic study. In 15-week-old male spontaneously hypertensive rats b (SHR), nifedipine (20mg/kg body weight/ day) (SHR-N) or lisinopril (5mg/kg body weight/day) (SHR-L) was given orally for 20 weeks and cardiac hypertrophy regressed with a significant decrease in hypertension. At 35 weeks of age, left ventricular (LV) function, blood neurohumoral factors and cellular architecture of LV wall were compared among SHR-N, SHR-L, and age-and sex-matched control SHR (SHR-C) and Wistar Kyoto rats (WKY). The animals were anesthetized with pentobarbital, a catheter was introduced into LV eavity via right carotid artery and LV pressure, its dp/dt and time constant T were recorded. Cardiac output was determined by the thermodilution method. Cardiac functional indexes at rest and during LV volume overloading were similar among SHR-N, L and C. Compared with SHR-C, plasma atrial natriuretic peptides and renin activity were significantly decreased in SHR-L and N, respectively. Scanning electron microsco
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py revealed that, in SHR-C, cardiocytes were thickened and elongated ; their lateral branches (LBs) multiplied and side-to-side junctions (SJs) were diminished in number. In SHR-N, cell width and LB number reduced with a mild blood pressure (BP) suppression, where as in SHR-L, cell width and length were diminished with a moderate BP supression, LBs were fewer and step-to-step junctions were more in number than in SHR-C. Cell size and junctions were comparable to those in 15week-old baseline SHR. Transmission electron microscopy revealed that, in SHR-C, intracellular volume fraction of myofibrils (Vmf) was decreased, mitochondria underwent degeneration and interstitial fibrosis was prominent. In both SHR-N and L, Vmf was similar to that in WKY, mitochondrial changes and interstitial fibrosis were apparently much less prominent than in SHR-C. These results suggest that in addition to antihypertensive effect, cardioprotective mechanisms of Ca-channel blocking with nifedipine and ACE inhibition with lisinopril may play a role for regression of cardiac hypertrophy and cellular remodeling.
Clinical study. LV mass was estimated by MRI and UCG method in patients with normal hearts and those with hypertrophied hearts. UCG method tended to overestimate left ventricular mass in both groups of the patients. MRI method seems to be relatively convenient and accurate to estimate cardiac mass, so that this method may be useful to evaluate regression of myocardial hypertrophy in human subjects. Less
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