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Inorganic Nitrate Supplementation Blunts Vasoconstrictor Responsiveness During Exercise in Patients with Type 2 Diabetes
Author(s) -
Bock Josh,
Hughes William,
Ueda Kenichi,
Feider Andrew,
Hanada Satoshi,
Casey Darren
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06458
Subject(s) - vasoconstriction , vasodilation , brachial artery , medicine , blood pressure , vascular resistance , anesthesia , endocrinology , cardiology
Patients with type 2 diabetes (T2D) have exaggerated α 1 ‐ and α 2 ‐vasoconstrictor responsiveness during exercise indicating reduced functional sympatholysis. Nitric oxide (NO) is purported to offset α‐mediated vasoconstriction during exercise (i.e., is sympatholytic). Given T2D have attenuated NO bioavailability, supplementation with inorganic nitrate (an exogenous source of NO) may reduce α 1 ‐ and/or α 2 ‐vasoconstrictor responsiveness during exercise in T2D. Thus, we examined if 8wks of inorganic nitrate supplementation (250mg daily, NO 3 group) reduced vasoconstrictor responsiveness to intra‐arterial infusions of phenylephrine (PE, α 1 ‐agonist) and/or dexmedetomidine (DEX, α 2 ‐agonist) during handgrip exercise in T2D relative to a placebo (PL group). Handgrip exercise trials lasted for 6min at 20% maximum grip strength. Steady‐state (SS) blood flow was achieved during the first 3min with either PE or DEX infused during the latter 3min. Forearm blood flow (FBF, ml/min) was calculated using brachial artery diameter and blood velocity measured via Doppler ultrasound. Forearm vascular conductance (FVC, ml/min/100mmHg), a surrogate of vasodilation, was calculated using FBF and mean arterial pressure (MAP). Both FBF and FVC were calculated from data averaged over the final 30sec of rest and SS exercise. Vasoconstrictor responsiveness for all trials was quantified as: ((SS FVC with drug − SS FVC pre‐drug )/SS FVC pre‐drug )x100%. The magnitude of sympatholysis was calculated as the difference in %vasoconstriction at rest and exercise for both α‐agonists. After baseline assessments, T2D were randomly assigned to the NO 3 (n=17, 13M/4F, 58±9yrs, 31.8±5.2kg/m 2 ) or PL (n=17, 12M/5F, 58±9yrs, 32.3±5.3kg/m 2 ) supplementation groups. Following supplementation, there were no differences in resting α 1 ‐ or α 2 ‐vasoconstrictor responsiveness observed between groups (group‐by‐time p =0.86 and 0.15, respectively). The NO 3 group had greater increases in FBF (164±68 to 185±70ml/min, p <0.05) and FVC (136±53 to 164±61ml/min/100mmHg, p <0.05) responses to exercise (Δ from rest) relative to the PL group (149±66 to 149±65ml/min and 129±64 to 133±60ml/min/100mmHg, p=0.93 and 0.59, respectively). No between‐group differences were observed for α 1 ‐mediated vasoconstrictor responsiveness during exercise or the corresponding magnitude of sympatholysis (group‐by‐time p =0.41 and 0.90, respectively). However, the NO 3 group had reduced α 2 ‐mediated vasoconstrictor responsiveness during exercise (−23.4±6.9 to −20.2±5.6% vs. −24.0±7.9 to −26.5±10.5%) with concomitant improvement in the magnitude of sympatholysis (−26.1±12.9 to −38.1±19.4 vs. −25.1±15.9 to −24.7±15.6) compared to the PL cohort, respectively ( p <0.05 for both). Principally, we found 8wks of inorganic nitrate supplementation augments the hyperemic (FBF) and vasodilatory (FVC) responses to exercise in T2D. Additionally, these beneficial effects could be attributable to decreased α 2 ‐mediated vasoconstrictor responsiveness in contracting skeletal muscle (i.e., improved functional sympatholysis). Support or Funding Information American Diabetes Association 1‐16‐1CTA‐015.