Skeletal Muscle Vascular Control During Exercise: Impact of Nitrite Infusion During Nitric Oxide Synthase Inhibition in Healthy Rats

The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2-) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2- infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3-6 months, n = 8) exercised without NG-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2- (7 mg kg(-1); L-NAME + NO2-). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L-NAME, NO2- infusion significantly reduced MAP (P < 0.03). The lower MAP in L-NAME+NO2- was not different from healthy control animals (control: 137 +/- 3 L-NAME: 157 +/- 7, L-NAME + NO2-: 136 +/- 5 mm Hg). Also, NO2- infusion significantly increased VC when compared to L-NAME (P < 0.03), ultimately negating any significant differences from control animals (control: 0.78 +/- 0.05, L-NAME: 0.57 +/- 0.03, L-NAME + NO2-; 0.69 +/- 0.04 mL min(-1) 100 g(-1) mm Hg-1) with no apparent fiber-type preferential effect. Overall, hindlimb BF was decreased significantly by L-NAME; however, in L-NAME + NO2-, BF improved to a level not significantly different from healthy controls (control: 108 +/- 8, L-NAME: 88 +/- 3, L-NAME + NO2-: 94 +/- 6 mL min(-1) 100 g(-1), P = 0.38 L-NAME vs L-NAME + NO2-). Individuals with diseases that impair NOS activity, and thus vascular function, may benefit from a NO2--based therapy in which NO bioavailability is elevated in an NOS-independent manner.