[Correction of cardiac functions in rats with experimental myocardial ischemia by chronic administration of endothelin-converting enzyme inhibitor].
Experiments on chronically instrumented Wistar rats demonstrated that 15 mm 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 (p < 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 decrease 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
VA
School of Biology, Lomonosov Moscow State University, Vorobjovy Gory, Russia. vikapet@fbm.msu.ru
Medvedeva
N A
NA
Khropov
Iu V
IuV
Pozdnev
V F
VF
Gomazkov
O A
OA
Medvedev
O S
OS
D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001794:Blood Pressure; D003331:Coronary Vessels; D003857:Deoxyuridine / Q000031:analogs & derivatives; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004617:Embolism / Q000150:complications; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate; D008297:Male; D008666:Metalloendopeptidases; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011412:Propanolamines; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*; D017725:Ventricular Pressure
D000318:Adrenergic beta-Agonists; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006146:Guanidines; D011412:Propanolamines; D013386:Succinates; C081648:5'-((N-(2-decanoylamino-3-hydroxy-3-phenylpropyloxycarbonyl)glycyl)amino)-5'-deoxyuridine; D009569:Nitric Oxide; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D003857:Deoxyuridine