1992 Fiscal Year Final Research Report Summary
MECHANISMS OF HEART FAILURE AND THE PROTECTIVE EFFECT BY ACE INHIBITOR
| Project/Area Number |
03670466
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
NOMA Kenji M.D.,Ph.D. DEPARTMENT OF INTERNAL MEDICINE, AOTO HOSPITAL, JIKEI UNIVERSITY SCHOOL OF MEDICINE, 医学部, 講師 (70130193)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Heart failure / Cardiac contraction / Myosin isoenzyme / ACE inhibitor / Vasodilator / Prostaglandin |
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| Research Abstract |
Heart failure was induced in male Wistar rats by combination of renovascular hypertension and arteriovenous shunt. Two weeks after operation,they were treated by captopril(1g/L) for 12 weeks. After treatment,the blood pressure(BP) and left ventricular(LV) weight were decreased. Isometric contraction of LV papillary muscle in captopril-treated rats showed a tendency to decrease in active tension and *dT/dtmax. Left ventricular myosin isoenzyme of treated rats showed significant change from V3 to V1. Subsequently, the heart failure model rats were treated by combination of prazosin(30mg/L) and isosorbide(ISDN,300mg/L), and captopril(1g/L) and indomethacin(55mg/L) which blocked prostaglandin. Prazosin-ISDN-treated rats showed a tendency to decrease in BP but no change in LV weight. Captopril-indomethacin-treated rats showed no change in BP except transient decrease in early stage of the treatment, and no change in LV weight. Isometric contraction and myosin isoenzyme of LV showed also no difference among prazosin-ISDN-treated, captopril-indomethacin-treated and non-treated rats.
From these results, it seemed to be insufficient for prevention of heart failure only to decrease after load and preload by prazosin and ISDN. It was suggested that prostaglandin was also as important as angiotensin 11 to the mechanisms of effect of captopril in the treatment of heart failure, because captopril alone showed the beneficial effect to protect heart failure, but the effect was vanished by combination with indomethacin. In addition, it should be taken into the consideration that the rats might take less amount of captopril in combination treatment compared with alone treatment, because these drugs were given as free drinking. We should also consider direct effect of ACE inhibitor to tissue renin-angiotensin system in the heart.
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