Effects of dietary L-arginine on the reactivity of canine coronary arteries.
Experiments were designed to determine the effects of supplemental dietary L-arginine 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 (alpha2-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 F2alpha, 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 alpha2-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.
Ray
E C
EC
Mayo Graduate School of Medicine, Mayo Foundation, Rochester, MN 55905, USA.
Landis
M E
ME
Miller
V M
VM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D019587:Dietary Supplements; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007476:Ionophores; D011810:Quinoxalines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D000068438:Brimonidine Tartrate; D019789:Tetraethylammonium; D001120:Arginine; D015237:Dinoprost