Department of Anatomy, Physiology & Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada.
PLoS One. 2023 Aug 1;18(8):e0289476. doi: 10.1371/journal.pone.0289476. eCollection 2023.
Oral L-arginine supplements are popular mainly for their nitric oxide mediated vasodilation, but their physiological impact is not fully known. L-arginine is a substrate of several enzymes including arginase, nitric oxide synthase, arginine decarboxylase, and arginine: glycine amidinotransferase (AGAT). We have published a study on the physiological impact of oral L- and D-arginine at 500 mg/kg/day for 4 wks in male Sprague-Dawley rats. We investigated the effects of oral L-arginine and D-arginine at a higher dose of 1000 mg/kg/d for a longer treatment duration of 16 wks in 9-week-old male Sprague-Dawley rats. We measured the expression and activity of L-arginine metabolizing enzymes, and levels of their metabolites in the plasma and various organs. L-arginine did not affect the levels of L-arginine and L-lysine in the plasma and various organs. L-arginine decreased arginase protein expression in the upper small intestine, and arginase activity in the plasma. It also decreased AGAT protein expression in the liver, and creatinine levels in the urine. L-arginine altered arginine decarboxylase protein expression in the upper small intestine and liver, with increased total polyamines plasma levels. Endothelial nitric oxide synthase protein was increased with D-arginine, the presumed metabolically inert isomer, but not L-arginine. In conclusion, oral L-arginine and D-arginine at a higher dose and longer treatment duration significantly altered various enzymes and metabolites in the arginine metabolic pathways, which differed from alterations produced by a lower dose shorter duration treatment published earlier. Further studies with differing doses and duration would allow for a better understanding of oral L-arginine uses, and evidence based safe and effective dose range and duration.
口服 L-精氨酸补充剂因其介导的一氧化氮血管舒张而广受欢迎，但它们的生理影响尚未完全了解。L-精氨酸是几种酶的底物，包括精氨酸酶、一氧化氮合酶、精氨酸脱羧酶和精氨酸：甘氨酸酰胺转移酶（AGAT）。我们已经发表了一项关于口服 L-和 D-精氨酸在雄性 Sprague-Dawley 大鼠中每天 500mg/kg 持续 4 周的生理影响的研究。我们研究了口服 L-精氨酸和 D-精氨酸在更高剂量 1000mg/kg/d 下更长治疗时间 16 周对 9 周龄雄性 Sprague-Dawley 大鼠的影响。我们测量了 L-精氨酸代谢酶的表达和活性及其代谢物在血浆和各种器官中的水平。L-精氨酸未影响血浆和各种器官中 L-精氨酸和 L-赖氨酸的水平。L-精氨酸降低了上小肠中的精氨酸酶蛋白表达和血浆中的精氨酸酶活性。它还降低了肝脏中的 AGAT 蛋白表达和尿液中的肌酐水平。L-精氨酸改变了上小肠和肝脏中的精氨酸脱羧酶蛋白表达，增加了总多胺的血浆水平。内皮型一氧化氮合酶蛋白随着 D-精氨酸增加，而 D-精氨酸是代谢惰性的异构体，但 L-精氨酸没有增加。总之，口服 L-精氨酸和 D-精氨酸在更高剂量和更长治疗时间下显著改变了精氨酸代谢途径中的各种酶和代谢物，这与早期发表的较低剂量较短治疗时间的改变不同。进一步的研究具有不同的剂量和持续时间将有助于更好地了解口服 L-精氨酸的用途，以及基于证据的安全有效剂量范围和持续时间。
