Voprosy meditsinskoi khimii (ISSN 0042-8809)

Correction of rat heart functional state after experimental myocardial ischemia in chronicle treatment with endothelin-converting enzyme inhibitor

   


1. School of Biology, Lomonosov Moscow State University
2. Institute of Biomedical Chemistry RAMS
3. School of Basic Medicine, Lomonosov Moscow State University
PubMed Id: 11075418
Year: 2000 vol: 46  issue:4  pages: 361-369
Abstract: Experiments on chronically instrumented Wistar rats demonstrated that 15mm microsphere embolization of coronary arteries led to a significant decrease in the systemic (APsyst) and maximal left ventricular systolic pressures (LVSPmax) to 10.1 and 21.1 % , respectively (р<0.05). To evaluate the role of endothelin in this pathology, the inhibitor of endothelin-converting enzyme (ECE), PP-36, was used. PP-36 abolished hemodynamic changes caused by embolization after 4 days per os treatment (starting 2 days before surgical procedure). Dobutamine test revealed marked decreas of LVSPmax and +dP/dtmax responses in the embolized versus sham operated animals. PP-36 normalized ischemical heart response to beta-adrenergic stimulation. Maximal APsyst and LVSPmax increases were observed in embolized rats. PP-36 abolished this effect and led to parallel rising reaction to aminoguanidin in embolized (APsyst: +12.4+1.6 vs. +6.8+2.3 mmHg, p<0.05) as well as in sham operated rats (APsyst: +8.5+1.1 vs. +5.6+0.7 mmHg, p<0.05). Thus, the present research showed the possibility to correct ischemical heart disturbance by using a new ECE inhibitor, PP-36. One possible mechanism of this drugs action may include systemic or myocardial changes in NO contribution to the maintenance of normal arterial pressure
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Reference: Petrukhina V.A., Medvedeva N.A., Khropov Y.V., Pozdnev V.F., Gomazkov O.A., Medvedev O.S., Correction of rat heart functional state after experimental myocardial ischemia in chronicle treatment with endothelin-converting enzyme inhibitor, Voprosy meditsinskoi khimii, 2000, vol: 46(4), 361-369.
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