Cardioprotective Effect against Ischemia-Reperfusion Injury of PAK-200, a Dihydropyridine Analog with an Inhibitory Effect on Cl- but Not Ca2+ Current.
Biomolecules
; 13(12)2023 11 29.
Article
em En
| MEDLINE
| ID: mdl-38136589
ABSTRACT
We examined the effects of a dihydropyridine analog, PAK-200, on guinea pig myocardium during experimental ischemia and reperfusion. In isolated ventricular cardiomyocytes, PAK-200 (1 µM) had no effect on the basal peak inward and steady-state currents but inhibited the isoprenaline-induced time-independent Cl- current. In the right atria, PAK-200 had no effect on the beating rate and the chronotropic response to isoprenaline. In an ischemia-reperfusion model with coronary-perfused right ventricular tissue, a decrease in contractile force and a rise in tension were observed during a period of 30-min no-flow ischemia. Upon reperfusion, contractile force returned to less than 50% of preischemic values. PAK-200 had no effect on the decline in contractile force during the no-flow ischemia but reduced the rise in resting tension. PAK-200 significantly improved the recovery of contractile force after reperfusion to about 70% of the preischemic value. PAK-200 was also shown to attenuate the decrease in tissue ATP during ischemia. Treatment of ventricular myocytes with an ischemia-mimetic solution resulted in depolarization of the mitochondrial membrane potential and an increase in cytoplasmic and mitochondrial Ca2+ concentrations. PAK-200 significantly delayed these changes. Thus, PAK-200 inhibits the cAMP-activated chloride current in cardiac muscle and may have protective effects against ischemia-reperfusion injury through novel mechanisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Di-Hidropiridinas
/
Traumatismo por Reperfusão Miocárdica
/
Isquemia Miocárdica
Limite:
Animals
Idioma:
En
Revista:
Biomolecules
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão