Cardioprotective effects of N-methylacetazolamide mediated by inhibition of L-type Ca 2+ channel current

• Published in: Biochimica et biophysica acta. General subjects 2022-05, Vol.1866 (5), p.130098
• Main Authors: Pardo, Alejandro Ciocci, Diaz Zegarra, Leandro A, González Arbeláez, Luisa F, Ibáñez, Alejandro M, Díaz, Romina G, Aiello, Ernesto A, Mosca, Susana M
• Format: Article
• Language: English
• Subjects: Animals; Calcineurin; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - metabolism; Cardiotonic Agents - pharmacology; Methazolamide - pharmacology; Myocardial Reperfusion Injury - metabolism; Myocytes, Cardiac - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats
• ISSN: 1872-8006

Our objective was to examine the effects of N-methylacetazolamide (NMA), a non‑carbonic anhydrase inhibitor, on ischemia-reperfusion injury. Isolated rat hearts were assigned to the following groups: 1) Non-ischemic control (NIC):110 min of perfusion and 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R). Both groups were repeated in presence of NMA (5 μM), administered during the first 10 min of R. Infarct size (IS) was measured by TTC staining. Developed pressure (LVDP) and end-diastolic pressure (LVEDP) of the left ventricle were used to assess systolic and diastolic function, respectively. The content of P-Akt, P-PKCε, P-Drp1 and calcineurin Aβ were measured. In cardiomyocytes the L-type Ca current (ICaL) was recorded with the whole-cell configuration of patch-clamp technique. The addition of NMA to non-ischemic hearts decreased 15% the contractility. In ischemic hearts (IC group), NMA decreased IS (22 ± 2% vs 32 ± 2%, p