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- Title
Cardioprotective Effect against Ischemia–Reperfusion Injury of PAK-200, a Dihydropyridine Analog with an Inhibitory Effect on Cl − but Not Ca 2+ Current.
- Authors
Namekata, Iyuki; Tamura, Miku; Kase, Jyunya; Hamaguchi, Shogo; Tanaka, Hikaru
- 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.
- Subjects
CALCIUM ions; REPERFUSION injury; DIHYDROPYRIDINE; RIGHT heart atrium; REPERFUSION; MYOCARDIUM
- Publication
Biomolecules (2218-273X), 2023, Vol 13, Issue 12, p1719
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom13121719