Effect of Histidine-Containing Dipeptides on Isolated Heart under Ischemia/Reperfusion

V. V. Alabovsky,¹ A. A. Boldyrev,^2,3 A. A. Vinokurov,¹ and V. Kh. Shchavratsky⁴

¹Department of Biochemistry, Voronezh Medical Academy, ul. Studencheskaya 10, Voronezh, 394622 Russia; E-mail: maslov@vgmi.voronezh.su

²Department of Biochemistry, School of Biology and International Biotechnology Center, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (7-095) 490-24-08; E-mail: aab@atpase.bio.msu.su

³To whom correspondence should be addressed.

⁴Laboratory of Neurochemistry, Institute of Neurology, Russian Academy of Medical Sciences, Volokolamskoe Shosse 80, Moscow, 123367 Russia; fax: (7-095) 490-24-08.

Submitted August 23, 1996; revision submitted September 19, 1996.

The protective effects of carnosine and related compounds on isolated rat heart were studied under experimental ischemia. The ability of carnosine to suppress significantly the development of ischemic reperfusion contracture and to support the restoration of the contractile force during reperfusion were shown. At the same time, a decrease of myoglobin and nucleoside release from myocytes was observed, this indicating a membrane-protecting effect of carnosine. Methylation of carnosine at the N1 or N3 atom of the imidazole ring significantly decreased the protective effect; the substitution of beta-alanine with gamma-aminobutyric acid (resulting in formation of homocarnosine) actually augmented ischemic damage to the heart. Acetylation of carnosine at the beta-amino group amplified the membrane-protecting properties of the molecule, the acetylated derivative of carnosine also showing the ability to induce contractile activity of the ischemic heart. Histidine alone or in combination with beta-alanine and sodium acetate had no effect, while acetylhistidine showed a significant protective effect during reperfusion. The comparison of the effects of natural histidine-containing dipeptides versus synthetic antioxidants indicates that the anti-ischemic effect of carnosine and acetylcarnosine involves antiradical and membrane-protecting mechanisms; nevertheless, the effect cannot be reduced to these mechanisms alone. The observed phenomena of heart muscle protection by acetylated derivatives of carnosine and anserine under ischemia correlates with the preferential localization of these compounds in high quantities in the myocardium.

KEY WORDS: histidine-containing dipeptides, ischemia, reperfusion, isolated heart.

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