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 N(G)-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.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA poole@vet.ksu.edu.
Scott K
SK
Ferguson
Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Angela A
AA
Glean
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Clark T
CT
Holdsworth
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Jennifer L
JL
Wright
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Alex J
AJ
Fees
Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Trenton D
TD
Colburn
Institute of Sport Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia.
Thomas
T
Stabler
Institute of Sport Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia.
Jason D
JD
Allen
Sport and Health Sciences, University of Exeter, St Luke's Campus, Exeter, United Kingdom.
Andrew M
AM
Jones
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
Timothy I
TI
Musch
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA Department of Kinesiology, Kansas State University, Manhattan, KS, USA.
David C
DC
Poole
D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009573:Nitrites / Q000008:administration & dosage*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D009573:Nitrites; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
blood flow; nitrate; nitric oxide; vascular control