Kynurenic acid influences the respiratory parameters of rat heart mitochondria

In the present study the effect of L-kynurenine, kynurenic acid and quinolinic acid on the heart mitochondrial function were investigated. Mitochondria were incubated with saturating concentrations of respiratory substrates glutamate/malate (5 mmol/l), succinate (10 mmol/l) or NADH (1 mmol/l), with and without kynurenines. The concentration of kynurenines varied between 1.25 micromol/l and 10 mmol/l. From all investigated kynurenines, only kynurenic acid affected dose-dependently the respiratory parameters of heart mitochondria. Respiratory control and P/O values were reduced significantly with glutamate/malate and moderately with succinate as substrates in the presence of 125 micromol/l to 10 mmol/l kynurenic acid. A known elevation of L-kynurenine in the blood of patients with ischemic heart disease or essential hypertension may suggest the involvement of L-kynurenine metabolites in the impairment of heart mitochondrial function, for example in cardiomyopathy.