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

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

We investigated the question of whether inhibition of the Na super(+)/H super(+) exchanger (NHE) during ischemia is protective due to reduction of cytosolic Ca super(2+) accumulation or enhanced acidosis in cardiomyocytes. Additionally, the role of the Na super(+)-HCO sub(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 super(2+) (fura 2), Na super(+) [sodium-binding benzolfuran isophthatlate (SBFI)], and cell length were measured. NHE was inhibited with 3 mu mol/1 HOE 642 or 1 mu mol/1 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 sub(i) and Ca sub(i), respectively) overload. During reoxygenation cells underwent hypercontracture (44.0 plus or minus 4.1% of the preanoxic length). During anoxia in bicarbonate buffer, inhibition of NHE had no effect on changes in intracellular pH (pH sub(i)), Na sub(i), and Ca sub(i), but it significantly reduced the reoxygenation-induced hypercontracture (HOE: 61.0 plus or minus 1.4%, EIPA: 68.2 plus or minus 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 sub(i) overload.