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

Petrukhina V.A.1, Medvedeva N.A.1, Khropov Y.V.1, Pozdnev V.F.2, Gomazkov O.A.2, Medvedev O.S.3

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  Volume: 46  Issue: 4  Pages: 361-369
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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Petrukhina V.A., Medvedeva N.A., Khropov Y.V., Pozdnev V.F., Gomazkov O.A., Medvedev O.S. (2000) Voprosy meditsinskoi khimii, 46(4), 361-369.
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