Low-dose L-arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats

Abstract

The objective of this work was to evaluate the influence of exogenous L-arginine on the capillary blood flow of peripheral tissues of normotensive subjects. Rats were anesthetized with sodium pentobarbital, and the blood flow of femoral, dorsal, and ventral skin and gastrocnemius and soleus muscle was measured by laser Doppler flow and microsphere methods to compare the blood flow before and after the L-arginine infusion. L-arginine lowered the mean blood pressure in a dose-dependent manner, but a statistically significant reduction in mean blood pressure was detected only at a high dose of 500 mg/kg of body weight. The significant blood flow increment was detected after the L-arginine infusion at doses of 50 and 150 mg/kg without causing hypotension. Nicardipine, a calcium channel blocker, also increased the skin blood flow, but the blood flow increment and blood pressure fall were comparable. A significant increment in microperfusion was detected in gastrocnemius, soleus muscle, and ventral skin compared with control group by the microsphere method. No adverse effects were observed during L-arginine and microsphere infusion. The present work indicates that l-arginine infusion increases muscle capillary blood flow in rats that are not performing exercise. Supplementation with l-arginine might provide additional blood flow at rest and during exercise and result in the improvement of muscle performance and exercise capacity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Recording of MBP, heart rate and blood flow, blood velocity, and blood mass of femoral skin during l-arginine (150 mg/kg for 30 min) infusion in one rat. Preinfusion values were recorded for >10 min before infusion to confirm stability, and the onset of recording is expressed as time 0. l-Arginine was infused from the 10-min to the 40-min period for 30 min, as indicated by the solid underbar.

Fig. 2.

Responses of MBP during l-arginine infusion at four different doses of 15, 50, 150, and 500 mg/kg, and nicardipine infusion at 0.4 μg/kg. Each column and vertical bar shows the mean ± SEM. ∗, P < 0.05; ∗∗, P < 0.01; significantly different vs. control value determined by factorial analysis of variance followed by Dunnet's test for mean values comparison.

Fig. 3.

Time course changes of femoral skin blood flow by using laser Doppler flow method and heart rate (HR) during l-arginine [Arg 15 (15 mg/kg l-arginine for 30 min), Arg 50 (50 mg/kg l-arginine for 30 min), Arg 150 (150 mg/kg l-arginine for 30 min), Arg 500 (500 mg/kg l-arginine for 30 min)] and nicardipine (Nic; 0.4 μg/kg nicardipine for 30 min) i.v. infusion. (Upper) Each point represents the percent change in MBF from preinfusion at 10-min intervals. (Lower) The individual values of mean heart rate at 10-min intervals are shown. Solid underbars represent sample infusion time. Data are illustrated as means ± SEM. ∗, P < 0.05; ∗∗, P < 0.01; significantly different vs. control value determined by factorial analysis of variance followed by Dunnet's test for mean values comparison.

Fig. 4.

Responses of blood velocity and blood mass in femoral skin during l-arginine infusion at four different doses of 15, 50, 150, and 500 mg/kg, and nicardipine infusion at a dose of 0.4 μg/kg. Each column and vertical bar shows the percent change from preinfusion values, and data are expressed as means ± SEM. ∗, P < 0.05; significantly different vs. control value determined by factorial analysis of variance followed by Dunnet's test for mean values comparison.

Fig. 5.

Effect of l-arginine infusion at doses of 50 and 150 mg/kg on regional blood flow. Each column and vertical bar shows the percent change from preinfusion values, and data are expressed as means ± SEM. ∗, Significant difference vs. preinfusion values, P < 0.05; †, significant difference vs. control group, P < 0.05.