Effects of dietary l-arginine on the reactivity of canine coronary arteries

Abstract

Experiments were designed to determine the effects of supplemental dietary l-argi-nine on the endothelial and smooth muscle function of canine coronary arteries. One group of dogs was fed the standard laboratory chow while another group was supplemented with 250 mg/kg per day l-arginine. All dogs had undergone bilateral reversed interposition saphenous vein grafting and received 325 mg/day oral aspirin. After 5 weeks of arginine feeding, left circumflex coronary arteries were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers. Concentration-response curves were obtained to l-arginine, UK-14,304 (a₂-adrenergic agonist) and A23187 (calcium ionophore) in the absence and presence of N^G-monomethyl-l-arginine (l-NMMA) and tetraethylammonium (TEA) alone or in combination.

Serum concentrations of l-arginine increased by about 20% following 2 weeks of arginine feeding and remained elevated throughout the study. In rings with and without endothelium contracted with prostaglandin F_{2 a}, l-arginine caused concentration-dependent contractions in rings from control animals but no significant change in tension in rings from arginine-fed animals. Contractions to l-arginine in control animals were reduced by either l-NMMA or TEA. Endothelium-dependent relaxations to the a₂-adrenergic agonist were decreased with arginine feeding while relaxations to the calcium ionophore and the endothelium-derived factor nitric oxide were similar among groups. Relaxations to UK-14,304 were reduced by l-NMMA in both groups but by TEA only in rings from control animals.

These results suggest that dietary supplementation with l-arginine modifies reactivity of endothelium and smooth muscle by at least two mechanisms: one associated with activation of potassium channels and the other with receptor-coupled release of nitric oxide.