L-Arginine and L-Citrulline Vasodilatory Effects

Mechanism of Action

• L-arginine is the sole substrate for nitric oxide synthase (NOS) enzymes, which produce nitric oxide, a potent vasodilator essential for maintaining normal vascular function 3, 4
• The vasodilatory effect occurs through the metabolism of L-arginine by NOS to produce NO, which causes relaxation of vascular smooth muscle 2, 3

Evidence for Vasodilatory Effects

L-Arginine Studies

• Short-term administration of L-arginine (500 mg/kg infused over 30 min) in pulmonary arterial hypertension (PAH) patients demonstrated a 15.8% reduction in mean pulmonary arterial pressure (mPAP) and 27% decrease in pulmonary vascular resistance (PVR) 5, 6
• Oral supplementation of L-arginine (0.5 g/10 kg body weight) in 19 PAH patients produced a 9% decrease in mPAP and 16% decrease in PVR 1, 7

Limitations and Inconsistencies

• Results have been mixed across studies, with some showing minimal effects on hemodynamics 1, 6
• A small study of acute L-arginine infusion in four IPAH patients demonstrated little favorable effect on pulmonary hemodynamics 1, 7
• Another short-term study of L-arginine infusion in normotensive volunteers and systemic sclerosis patients with PAH showed no significant effect on hemodynamics 1, 7

Clinical Implications

• Despite growing use of oral arginine supplements, rigorous randomized trials of long-term oral arginine supplementation in relevant patient populations are lacking 1, 8
• Potential drawbacks of arginine supplementation may include increased concentration of proproliferative polyamines 1, 8
• The short-term vasodilatory effects observed in controlled settings may not necessarily translate to long-term benefits 1, 8