Skeletal Muscle Vascular Control During Exercise

Autor: Alexander J. Fees, Trenton D. Colburn, Timothy I. Musch, Angela A. Glean, Andrew M. Jones, Thomas Stabler, Jason D. Allen, Clark T. Holdsworth, David C. Poole, Scott K. Ferguson, Jennifer Wright
Rok vydání: 2015
Předmět:
Zdroj: Journal of Cardiovascular Pharmacology and Therapeutics. 21:201-208
ISSN: 1940-4034
1074-2484
Popis: 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.
Databáze: OpenAIRE