Plasma l-citrulline concentrations in l-arginine–supplemented healthy dogs

• Published in: Journal of veterinary cardiology Vol. 19; no. 4; pp. 376 - 383
• Main Authors: Flynn, K.M., Kellihan, H.B., Trepanier, L.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2017
• Subjects: Animals; Arginine - administration & dosage; Blood Pressure; Canine; Citrulline - blood; Dogs - blood; eNOS; Female; Male; Nitric Oxide; Pulmonary hypertension; Sildenafil; eNOS; Sildenafil; Nitric oxide; Pulmonary hypertension; Canine
• ISSN: 1760-2734; 1875-0834
• DOI: 10.1016/j.jvc.2017.04.005

To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). – Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25–30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2–231.4 μM) to a peak of 417.4 μM (206.5–807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1–117.1 μM) to peak of 102.2 μM (47.4–192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25–30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. – Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted.