PMID- 34718145
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20220221
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 118
DP  - 2022 Jan 1
TI  - Combined inorganic nitrate/nitrite supplementation blunts alpha-mediated 
      vasoconstriction during exercise in patients with type 2 diabetes.
PG  - 17-25
LID - S1089-8603(21)00110-5 [pii]
LID - 10.1016/j.niox.2021.10.006 [doi]
AB  - AIMS: Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory 
      responses during exercise partially attributable to low nitric oxide (NO) levels. 
      Low NO contributes to greater alpha-adrenergic mediated vasoconstriction in 
      contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks 
      of active beetroot juice (BR(A), 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) 
      improves hyperemia, via reduced alpha-mediated vasoconstriction, during handgrip 
      exercise relative to nitrate/nitrite-depleted beetroot juice (BR(P), n = 18) in 
      patients with T2DM. METHODS: Forearm blood flow (FBF) and vascular conductance 
      (FVC) were calculated at rest and during handgrip exercise (20%max, 
      20contractions.min(-1)). Phenylephrine (alpha(1)-agonist) and dexmedetomidine 
      (alpha(2)-agonist) were infused intra-arterially during independent trials to 
      determine the influence of alpha-mediated vasoconstriction on exercise hyperemia. 
      Vasoconstriction was quantified as the percent-reduction in FVC during alpha-agonist 
      infusion, relative to pre-infusion, as well as the absolute change in %FVC during 
      exercise relative to the respective rest trial (magnitude of sympatholysis). 
      RESULTS: DeltaFBF (156 +/- 69 to 175 +/- 73 ml min(-1)) and DeltaFVC (130 +/- 54 to 
      156 +/- 63 ml min(-1).100 mmHg(-1), both P < 0.05) during exercise were augmented 
      following BR(A), but not BR(P) (P = 0.96 and 0.51). Phenylephrine-induced 
      vasoconstriction during exercise was blunted following BR(A) (-17.1 +/- 5.9 to 
      -12.6 +/- 3.1%, P < 0.01), but not BR(P) (P = 0.58) supplementation; the magnitude 
      of sympatholysis was unchanged by either (beverage-by-time P = 0.15). BR(A) 
      supplementation reduced dexmedetomidine-induced vasoconstriction during exercise 
      (-23.3 +/- 6.7 to -19.7 +/- 5.2%) and improved the corresponding magnitude of 
      sympatholysis (25.3 +/- 11.4 to 34.4 +/- 15.5%, both P < 0.05). CONCLUSIONS: BR(A) 
      supplementation improves the hyperemic and vasodilatory responses to exercise in 
      patients with T2DM which appears to be attributable to reduced alpha-adrenergic 
      mediated vasoconstriction in contracting skeletal muscle.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Bock, Joshua M
AU  - Bock JM
AD  - Department of Physical Therapy and Rehabilitation Science, Carver College of 
      Medicine, University of Iowa, Iowa City, IA, USA.
FAU - Ueda, Kenichi
AU  - Ueda K
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, 200 
      Hawkins Dr, Iowa City, IA, USA.
FAU - Feider, Andrew J
AU  - Feider AJ
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, 200 
      Hawkins Dr, Iowa City, IA, USA.
FAU - Hanada, Satoshi
AU  - Hanada S
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, 200 
      Hawkins Dr, Iowa City, IA, USA.
FAU - Casey, Darren P
AU  - Casey DP
AD  - Department of Physical Therapy and Rehabilitation Science, Carver College of 
      Medicine, University of Iowa, Iowa City, IA, USA; Abboud Cardiovascular Research 
      Center, University of Iowa, 285 Newton Rd, Iowa City, IA, USA; Fraternal Order of 
      Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, 169 Newton 
      Rd, IA, USA. Electronic address: darren-casey@uiowa.edu.
LA  - eng
GR  - P30 CA086862/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211027
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Adrenergic alpha-1 Receptor Agonists)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 1WS297W6MV (Phenylephrine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 67VB76HONO (Dexmedetomidine)
SB  - IM
MH  - Adrenergic alpha-1 Receptor Agonists/pharmacology
MH  - Aged
MH  - Beta vulgaris/chemistry
MH  - Dexmedetomidine/pharmacology
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Dietary Supplements
MH  - Exercise/*physiology
MH  - Female
MH  - Fruit and Vegetable Juices
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/drug effects
MH  - Nitrates/*pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitrites/*pharmacology
MH  - Phenylephrine/pharmacology
MH  - Plant Roots/chemistry
MH  - Vasoconstriction/*drug effects
OTO - NOTNLM
OT  - Blood flow
OT  - Diabetes
OT  - Exercise
OT  - Nitric oxide
OT  - Vasodilation
EDAT- 2021/11/01 06:00
MHDA- 2022/02/22 06:00
CRDT- 2021/10/31 20:49
PHST- 2021/08/25 00:00 [received]
PHST- 2021/10/21 00:00 [revised]
PHST- 2021/10/25 00:00 [accepted]
PHST- 2021/11/01 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/10/31 20:49 [entrez]
AID - S1089-8603(21)00110-5 [pii]
AID - 10.1016/j.niox.2021.10.006 [doi]
PST - ppublish
SO  - Nitric Oxide. 2022 Jan 1;118:17-25. doi: 10.1016/j.niox.2021.10.006. Epub 2021 
      Oct 27.