CARDIOPROTECTION OF BENZOLAMIDE IN A REGIONAL ISCHEMIA MODEL: ROLE OF eNOS/NO

FANTINELLI JC; SWENSON ER; GONZÁLEZ ARBELÁEZ LF; ALVAREZ BV; CIOCCI PARDO, A; MOSCA SM

Mar del Plata, Buenos Aires

Congreso; SAIC.SAI.SAFIS 2018; 2018

Recent studies from our laboratory show the cardioprotective actionof benzolamide (BZ, carbonic anhydrase inhibitor) againstischemia-reperfusion injury. However, the mechanisms involvedhave not been fully elucidated. To examine the participation of theendothelial nitric oxide synthase (eNOS)/nitric oxide (NO) in theeffects of BZ in a model of regional ischemia. Isolated rat heartsperfused by Langendorff technique were submitted to 40 min ofcoronary artery occlusion followed by 60 min of reperfusion (IC).Other hearts received BZ during the first 10 min of reperfusion inabsence or presence of L-NAME, NOS inhibitor. The infarct size (IS)and the post-ischemic recovery of myocardial function were measured.Oxidative/nitrosative damage were assessed by reducedglutathione (GSH) content, thiobarbituric acid reactive substances(TBARS) and 3-nitrotyrosine levels. The expression of phosphorylatedforms of Akt, p38MAPK, eNOS and iNOS were also determined.BZ significantly decreased IS (6.2 ± 0.5% vs. 34 ± 4% inIC), improved post-ischemic contractility, preserved GSH levels (3.4± 0.4 vs. 2.0 ± 0.31 μg/mg prot) and diminished TBARS (0.49 ±0.06 vs. 0.74 ± 0.04 nmol/mg prot) and 3-nitrotyrosine (84 ± 5% vs.127 ± 4%). In IC hearts, P-Akt, P-p38MAPK and P-eNOS decreased(71± 1%, 26 ± 6% and 57 ± 2%, respectively) and iNOS increased(122 ± 1%). After BZ addition the levels of P-kinases and P-eNOSincreased (132 ± 1%, 122 ± 1%, 118 ± 5% for P-Akt, P-p38MAPKand P-eNOS, respectively) and iNOS decreased (84 ± 2%). Exceptfor P-Akt, P-p38MAPK and iNOS, the effects of BZ were abolishedby L-NAME. Our data demonstrate that the treatment with BZ at theonset of reperfusion was effective to reduce cell death, contractiledysfunction and oxidative/nitrosative damage produced by coronaryartery occlusion. These BZ-mediated beneficial actions appear mediatedby eNOS/NO-dependent pathways