L-arginine potentiates negative inotropic and metabolic effects to myocardium partly through the amiloride sensitive mechanism.

Recently, cytokines have been proposed to cause cellular injury by nitric oxide (NO.) mediated pathway and L-arginine has been proposed to impair intracellular pH (pH(i)) regulation via vacuolar type H(+)-ATPase in macrophage. We conducted this investigation on Langendorff perfused hearts of rabbits to elucidate the mechanisms involving the NO. precursor L-arginine on myocardial contractile function, glycolysis, mitochondrial respiration, and intracellular alkalinization and tested the effects of amiloride. L-Arginine caused a significant loss of contractile function (96+/-4 mmHg in control, 53+/-16 during L-arginine perfusion, p<0.01) and a significant increase of pH(i) (7.01+/-0.02 prearginine infusion, 7.08+/-0.03 at the end of L-arginine infusion, p<0.01) along with decreased oxygen consumption (MVO(2)) (0.94+/-0.32 ml/min/g dry wt.), increased lactate release, and a loss of creatine phosphate (15% loss). Amiloride could prevent the cell alkalinization and contractile dysfunction, but not the derangement of oxidative metabolism caused by L-arginine in myocytes. We conclude that L-arginine has two distinct effects upon the myocardium: (1) an amiloride-sensitive loss of contractile function associated with intracellular alkalinization; and (2) an amiloride-insensitive inhibition of oxidative metabolism, possibly because of increased myocardial NO. production.