Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans

Holowatz, Lacy A.; Kenney, W. Larry

doi:10.1152/ajpheart.00295.2007

Cited by 91 publications

(88 citation statements)

References 39 publications

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“…Although we found local lines with slopes equal to 1, these lines did not shift in parallel in both anatomical locations; volar region and gaiter area. These findings suggest that the local vascular functions are impaired in volar region and in gaiter area in EHT patients and are in agreement with the finding of existing literature (1)(2)(3)(4)(5)(6). Under pathological condition such as EHT, remodeling can eventually compromise vessel elasticity.…”

Section: Local Regionsupporting

confidence: 92%

“…In the last two decade, studies on human cutaneous circulation have provided extensive data to assess microvascular function in a variety of vascular disease states including hypertension (1)(2)(3)(4)(5)(6). Although the skin blood flow measured from the volar region of the forearm has been commonly used to assess microvascular function in humans, the gaiter area (proximal to the medial malleolus) in the leg can also be used as an appropriate measurement site in some specific diseases.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

Esen¹,

Ata²,

Esen³

2013

Anadolu Kardiyol Derg

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Objective: To investigate limb specific differences in cutaneous vascular function in patients (n=33) with essential hypertension (EHT). Methods: In this observational cross-sectional study, baseline skin blood flow and the response to local heating were measured with a laser Doppler flowmeter (LDF) from the volar region of the forearm and the gaiter area of the foot at supine rest. The fractal analysis, detrended fluctuation analysis (DFA), was used to calculate the correlation properties of skin blood flow, LDF signal. The paired t-test and repeated measures ANOVA were used to determine the response to local heating and compare the scaling exponents of different anatomical locations respectively. Results: We found three linear scaling regions that describe the fractal behavior of LDF signal with their slopes, scaling exponents. For cardiac (α C ) and cardio-respiratory (α CR ) scaling exponents, thermal hyperemia (T) induced greater change in the leg (α C =1.49±0.26; α CT =1.62±0.20 p<0.01 and α CR =0.84±0.29 α CRT =0.42±0.28 p<0.001) than in forearm (α C =1.28±0.13; α CT =1.33±0.13 p>0.05 and α CR =0.73±0.15; α CRT =0.65±0.018 p<0.05). Local scaling exponents (α L ≈α LT~1 ) were not significantly different (p>0.05) and, local lines did not shift in parallel with local heating in both extremities. Conclusion:The results of the present study suggest that skin microvascular function is impaired in both extremities in EHT patients. However, myogenic response is not uniform in both extremities and pronounced response to local thermal hyperemia has been observed in the gaiter area compared with the volar region. Further studies are needed to determine if these limb specific microvascular differences is the result of posture-induced structural and functional adaptation. (Anadolu Kardiyol Derg 2014; 14: 3-8)

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Section: Local Regionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

Esen¹,

Ata²,

Esen³

2013

Anadolu Kardiyol Derg

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“…Protocols were performed in a thermoneutral laboratory with the subjects in a supine position. Four intradermal microdialysis fibers (MD 2000; Bioanalytical Systems) (10 mm, 20-kDa cutoff membrane) were inserted as previously described (9) in the ventral forearm, abdomen, thigh, and lower back. Foam was placed underneath the subject to prevent pressure being placed on the equipment and the measurement site at the lower back.…”

Section: Instrumentationmentioning

confidence: 99%

Nonuniform, age-related decrements in regional sweating and skin blood flow

Smith

Alexander

Kenney

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Smith CJ, Alexander LM, Kenney WL. Nonuniform, age-related decrements in regional sweating and skin blood flow. Am J Physiol Regul Integr Comp Physiol 305: R877-R885, 2013. First published August 7, 2013 doi:10.1152/ajpregu.00290.2013.-Aging is associated with attenuated thermoregulatory function that varies regionally over the body. Decrements in vasodilation and sweating are well documented with age, yet limited data are available concerning the regional relation between these responses. We aimed to examine age-related alterations in the relation between regional sweating (RSR) and skin blood flow (SkBF) to thermal and pharmacological stimuli. Four microdialysis fibers were inserted in the ventral forearm, abdomen, thigh, and lower back of eight healthy aged subjects (64 Ϯ 7 yr) and nine young (23 Ϯ 3 yr) during 1) ACh dose response (1 ϫ 10 Ϫ7 to 0.1 M, mean skin temperature 34°C) and 2) passive whole body heating to ⌬1°C rise in oral temperature (Tor). RSR and SkBF were measured over each microdialysis membrane using ventilated capsules and laser-Doppler flowmetry. Maximal SkBF was measured at the end of both protocols (50 mM SNP). Regional sweating thresholds and RSR were attenuated in aged vs. young at all sites (P Ͻ 0.0001) during whole body heating. Vasodilation thresholds were similar between groups (P Ͼ 0.05). Attenuated SkBF were observed at the arm and back in the aged, representing 56 and 82% of those in the young at these sites, respectively (0.5 ⌬Tor). During ACh perfusion, SkBF (P ϭ 0.137) and RSR were similar between groups (P ϭ 0.326). Together these findings suggest regional age-related decrements in heat-activated sweat gland function but not cholinergic sensitivity. Functional consequences of such thermoregulatory impairment include the compromised ability of older individuals to defend core temperature during heat exposure and a subsequently greater susceptibility to heat-related illness and injury.sweating; aging; laser-Doppler flowmetry; skin blood flow; sweating HUMAN AGING IS ASSOCIATED with altered thermoregulatory function during both passive and exercise-induced hyperthermia, including attenuated reflex cutaneous vasodilation (26) and eccrine sweating responses (3,18,24). A functional loss of active cholinergic vasodilation cotransmitter function and dysfunction of second-messenger pathways (i.e., nitric oxide bioavailability) (8,11,12,31) contribute to attenuated cutaneous vasodilatory responses to elevations in core temperature (T core ), hindering convective heat loss. An age-related decline in thermoregulatory sweating further compromises heat loss and increases thermal strain in warm ambient conditions and during exercise. Reduced evaporative heat loss from the skin surface results from a decline in thermoregulatory sweating, due to a decreased thermal sensitivity (32) and atrophy of the sweat glands (17, 19), producing a lower sweat output per gland (23,24,39).Regional variation in sweating and skin blood flow (SkBF) responses to passive heating are well documented (29); howev...

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“…The plateau phase is nitric oxide (NO) dependent (17,19). It has been used to evaluate NO bioavailability (15,26,32). Recently, we observed that plasma angiotensin II (ANG II) is increased in a subset of patients with postural tachycardia syndrome (POTS) (25,27) in whom we demonstrated blunted cutaneous microvascular NO-dependent vasodilation to local heat (18).…”

mentioning

confidence: 99%

Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

Stewart

Taneja²,

Raghunath³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The vasodilation response to local cutaneous heating is nitric oxide (NO) dependent and blunted in postural tachycardia but reversed by angiotensin II (ANG II) type 1 receptor (AT1R) blockade. We tested the hypothesis that a localized infusion of ANG II attenuates vasodilation to local heating in healthy volunteers. We heated the skin of a calf to 42°C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance (%CVCmax) in eight healthy volunteers aged 19.5-25.5 years. Initially, two experiments were performed; in one, Ringer solution was perfused in three catheters, the response to heating was measured, 2 g/l losartan, 10 mM nitro-L-arginine (NLA), or NLA ϩ losartan was added to perfusate, and the heat response was remeasured; in another, 10 M ANG II was given, the heat response was measured, losartan, NLA, or NLA ϩ losartan was added to ANG II, and the heat response was reassessed. The heat response decreased with ANG II, particularly the plateau phase (47 Ϯ 5 vs. 84 Ϯ 3 %CVC max). Losartan increased baseline conductance in both experiments (from 8 Ϯ 1 to 20 Ϯ 2 and 12 Ϯ 1 to 24 Ϯ 3). Losartan increased the ANG II response (83 Ϯ 4 vs. 91 Ϯ 6 in Ringer). NLA decreased both angiotensin and Ringer responses (31 Ϯ 4 vs. 43 Ϯ 3). NLA ϩ losartan blunted the Ringer response (48 Ϯ 2), but the ANG II response (74 Ϯ 5) increased. In a second set of experiments, we used dose responses to ANG II (0.1 nM to 10 M) with and without NLA ϩ losartan to confirm graded responses. Sodium ascorbate (10 mM) restored the ANG II-blunted heating plateau. NO synthase and AT 1R inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT1R blunting of local heating, which is not exclusively NO dependent, and is improved by antioxidant supplementation. lasers; conductance; skin THE VASODILATION RESPONSE of nonglabrous skin to local heating can be described in terms of distinct phases including an initial thermal peak, a decrease to a nadir, and an increase to a plateau (17,19). The plateau phase is nitric oxide (NO) dependent (17,19). It has been used to evaluate NO bioavailability (15,26,32). Recently, we observed that plasma angiotensin II (ANG II) is increased in a subset of patients with postural tachycardia syndrome (POTS) (25,27) in whom we demonstrated blunted cutaneous microvascular NO-dependent vasodilation to local heat (18). We further demonstrated that ANG II type 1 receptor (AT 1 R) blockade with losartan corrects the cutaneous NO deficit in these patients (26). This is consistent with ANG II vasoconstrictive capabilities including the ability to produce direct smooth muscle vasoconstriction (30). However, one of the most potent vasoconstrictive actions of ANG II is mediated by AT 1 R-dependent interactions with NADPH oxidase, resulting in an enhanced production of reactive oxygen species (ROS) (11-13). One such ROS is superoxide, which scavenges and combines with NO to produce peroxynitrite (21). Thus a potent oxidative/nitrative agent i...

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Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans

Cited by 91 publications

References 39 publications

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

Nonuniform, age-related decrements in regional sweating and skin blood flow

Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

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