Inhibition of NHE protects reoxygenated cardiomyocytes independently of anoxic Ca 2+ overload and acidosis

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 279; no. 5; pp. H2143 - H2150
• Main Authors: Schäfer, C., Ladilov, Y. V., Schäfer, M., Piper, H. M.
• Format: Journal Article
• Language: English
• Published: 01.11.2000
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.5.H2143

We investigated the question of whether inhibition of the Na + /H + exchanger (NHE) during ischemia is protective due to reduction of cytosolic Ca 2+ accumulation or enhanced acidosis in cardiomyocytes. Additionally, the role of the Na + -HCO 3 − symporter (NBS) was investigated. Adult rat cardiomyocytes were exposed to simulated ischemia and reoxygenation. Cytosolic pH [2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)], Ca 2+ (fura 2), Na + [sodium-binding benzolfuran isophthatlate (SBFI)], and cell length were measured. NHE was inhibited with 3 μmol/l HOE 642 or 1 μmol/l 5-( N-ethyl- N-isopropyl)-amiloride (EIPA), and NBS was inhibited with HEPES buffer. During anoxia in bicarbonate buffer, cells developed acidosis and intracellular Na and Ca (Na i and Ca i , respectively) overload. During reoxygenation cells underwent hypercontracture (44.0 ± 4.1% of the preanoxic length). During anoxia in bicarbonate buffer, inhibition of NHE had no effect on changes in intracellular pH (pH i ), Na i , and Ca i , but it significantly reduced the reoxygenation-induced hypercontracture (HOE: 61.0 ± 1.4%, EIPA: 68.2 ± 1.8%). The sole inhibition of NBS during anoxia was not protective. We conclude that inhibition of NHE during anoxia protects cardiomyocytes against reoxygenation injury independently of cytosolic acidification and Ca i overload.