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
Petrukhina V.A. и др., Correction of rat heart functional state after experimental myocardial ischemia in chronicle treatment with endothelin-converting enzyme inhibitor //Voprosy meditsinskoi khimii.- 2000. -Т.46. -№ 4. С. 361-369.
Petrukhina V.A. и др., "Correction of rat heart functional state after experimental myocardial ischemia in chronicle treatment with endothelin-converting enzyme inhibitor." Voprosy meditsinskoi khimii 46.4 (2000): 361-369.
Petrukhina V.A., Medvedeva N.A., Khropov Y.V., Pozdnev V.F., Gomazkov O.A., Medvedev O.S. (2000). Correction of rat heart functional state after experimental myocardial ischemia in chronicle treatment with endothelin-converting enzyme inhibitor. Voprosy meditsinskoi khimii, 46(4), 361-369.