scholarly journals Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans

2013 ◽  
Vol 305 (4) ◽  
pp. R452-R458 ◽  
Author(s):  
Jessica D. Dahmus ◽  
Rebecca S. Bruning ◽  
W. Larry Kenney ◽  
Lacy M. Alexander
Keyword(s):  
Local Heating ◽  
Reactive Hyperemia ◽  
Area Under The Curve ◽  
Control Site ◽  
Microvascular Function ◽  
Sensory Nerves ◽  
Controlled Study ◽  
Double Blind ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation

Platelet P2Y12-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P > 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.

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

2007 ◽  
Vol 293 (2) ◽  
pp. H1090-H1096 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Local Heating ◽  
Oxidant Stress ◽  
Control Site ◽  
No Synthase ◽  
Oral Temperature ◽  
Antioxidant Supplementation ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Reflex Cutaneous Vasodilation ◽  
Cutaneous Vascular Conductance

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated with essential hypertension. Decreased NO-dependent VD may be due to 1) increased oxidant stress and/or 2) decreased l-arginine availability through upregulated arginase activity, potentially leading to increased superoxide production through uncoupled NO synthase (NOS). The purpose of this study was to determine the effect of antioxidant supplementation (alone and combined with arginase inhibition) on attenuated NO-dependent reflex cutaneous VD in hypertensive subjects. Nine unmedicated hypertensive [HT; mean arterial pressure (MAP) = 112 ± 1 mmHg] and nine age-matched normotensive (NT; MAP = 81 ± 10 mmHg) men and women were instrumented with four intradermal microdialysis (MD) fibers: control (Ringer), NOS inhibited (NOS-I; 10 mM NG-nitro-l-arginine), l-ascorbate supplemented (Asc; 10 mM l-ascorbate), and Asc + arginase inhibited [Asc+A-I; 10 mM l-ascorbate + 5 mM ( S)-(2-boronoethyl)-l-cysteine-HCl + 5 mM Nω-hydroxy- nor-l-arginine]. Oral temperature was increased by 0.8°C via a water-perfused suit. NG-nitro-l-arginine was then ultimately perfused through all MD sites to quantify the change in VD due to NO. Red blood cell flux was measured by laser-Doppler flowmetry over each skin MD site, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/MAP) and normalized to maximal CVC (%CVCmax; 28 mM sodium nitroprusside + local heating to 43°C). During the plateau in skin blood flow (ΔTor = 0.8°C), cutaneous VD was attenuated in HT skin (NT: 42 ± 4, HT: 35 ± 3 %CVCmax; P < 0.05). Asc and Asc+A-I augmented cutaneous VD in HT (Asc: 57 ± 5, Asc+A-I: 53 ± 6 %CVCmax; P < 0.05 vs. control) but not in NT. %CVCmax after NOS-I in the Asc- and Asc+A-I-treated sites was increased in HT (Asc: 41 ± 4, Asc+A-I: 40 ± 4, control: 29 ± 4; P < 0.05). Compared with the control site, the change in %CVCmax within each site after NOS-I was greater in HT (Asc: −19 ± 4, Asc+A-I: −17 ± 4, control: −9 ± 2; P < 0.05) than in NT. Antioxidant supplementation alone or combined with arginase inhibition augments attenuated reflex cutaneous VD in hypertensive skin through NO- and non-NO-dependent mechanisms.

Abstract 209: NAD(P)H Oxidase-Derived Superoxide Contributes to Impaired Cutaneous Microvascular Function in Chronic Kidney Disease

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jennifer J DuPont ◽  
Meghan G Ramick ◽  
William B Farquhar ◽  
Raymond R Townsend ◽  
David G Edwards
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Xanthine Oxidase ◽  
Local Heating ◽  
Control Site ◽  
Healthy Control Group ◽  
Control Group ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Healthy Control

Endothelial dysfunction occurs in chronic kidney disease (CKD) and cardiovascular disease is the most common cause of death in these patients. Oxidative stress has been shown to be a mechanism of vascular dysfunction in CKD. We utilized the cutaneous circulation to test the hypothesis that superoxide derived from NAD(P)H oxidase and xanthine oxidase impair nitric oxide (NO)-dependent cutaneous vasodilation patients with CKD. Twenty subjects, 10 stage 3 and 4 CKD patients (61±4 years; 5 male/5 female; eGFR: 39 ± 4 ml·min -1 ·1.73m -2 ) and 10 healthy controls (HC) (55±2 years; 4 male/6 female; eGFR: >60 ml·min -1 ·1.73m -2 ) were instrumented with 4 intradermal microdialysis fibers in the forearm for the local delivery of 1) Ringers solution (Control), 2) 10 μM Tempol to scavenge superoxide, 3) 100 μM apocynin to inhibit NAD(P)H oxidase, and 4) 10 μM allopurinol to inhibit xanthine oxidase. Red blood cell (RBC) flux was measured via laser Doppler flowmetry during standardized local heating (42°C). After the local heating response was established, 10 mM L-NAME was infused into all four sites to quantify the NO-dependent portion of the response. Cutaneous vascular conductance (CVC) was calculated as RBC flux/mean arterial pressure and all data are presented as a percentage of maximum CVC achieved during 28mM sodium nitroprusside infusion at 43°C. The plateau in cutaneous vasodilation was attenuated in CKD at the control site (CKD: 77±3 vs. HC: 88±3 %, p<0.05). Tempol and apocynin augmented the plateau in cutaneous vasodilation in CKD patients (Tempol: 88±2, apocynin: 91±2 %, p<0.05 vs. CKD control site) but had no effect in the healthy control group. The NO-dependent portion of the response was reduced in CKD at the control site (CKD: 41±4 vs. HC: 58±2 %, p<0.05). Tempol and apocynin augmented NO-dependent portion of the response in CKD patients (Tempol: 58±3, apocynin: 58±4 %, p<0.05 vs. CKD control site) but had no effect in the healthy control group. Inhibition of xanthine oxidase did not alter the plateau in cutaneous vasodilation in either group (p>0.05). These data suggest that NAD(P)H oxidase is a source of superoxide and contributes to microvascular dysfunction in CKD.

Abstract P276: A High Sodium Diet Reduces Cutaneous Microvascular Function In Normotensive Individuals With Salt Sensitive Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jordan C Patik ◽  
Joseph M Stock ◽  
Nathan T Romberger ◽  
Shannon L Lennon ◽  
William B Farquhar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Sodium Intake ◽  
Local Heating ◽  
Urinary Sodium Excretion ◽  
Microvascular Function ◽  
Dietary Sodium ◽  
Heating Unit ◽  
Doppler Flowmetry ◽  
High Sodium

Impaired vascular function likely contributes to the association between dietary sodium intake and the development of cardiovascular disease. Using the cutaneous microvasculature as a model, we have previously shown that a high sodium (HS) diet blunts local heating-induced vasodilation in normotensive individuals with salt resistant (SR) blood pressure (BP). However, the effect of a HS diet on the cutaneous microvasculature in normotensive salt sensitive (SS) individuals remains unclear. Therefore, we tested the hypothesis that cutaneous microvascular function is reduced by a HS diet to a greater degree in SS compared to SR individuals. After each 7-day controlled feeding diet (low sodium (LS) = 20 mmol/day; HS = 300 mmol/day), an intradermal microdialysis fiber was inserted in the ventral forearm and perfused with Ringer’s solution. Skin blood flow (SkBF) was continuously monitored via laser Doppler flowmetry and a local heating unit was placed over the fiber and heated to 42°C until SkBF reached a stable plateau. Site-specific maximal SkBF was determined by perfusing 28mM sodium nitroprusside and heating to 43°C. Mean arterial pressure (MAP) was assessed at regular intervals on the contralateral arm and was used to calculate cutaneous vascular conductance (CVC = SkBF / MAP). Subjects wore a 24-hr ambulatory BP monitor and collected their urine on the final day of each diet. Fourteen subjects (9W / 5M, 42 ± 14 yr) whose MAP increased >5 mmHg (Δ8 ± 1 mmHg) on the HS diet were defined as SS and were compared to 14 age- (43± 14 yr) and sex-matched SR subjects (Δ1 ± 3 mmHg). SS and SR had similar MAP at baseline (88 ± 9 vs. 90 ± 8 mmHg, P = 0.88) and urinary sodium excretion was increased similarly across groups by the HS diet (Δ239 ± 104 vs. Δ220 ± 66 mmol / 24 hr, P = 0.20). Cutaneous vasodilation in response to local heating was decreased on the HS diet relative to the LS diet in both SS (Δ-9 ± 9 %CVCmax, P = 0.005) and SR (Δ-9 ± 9 %CVCmax, P=0.005); however, there was not a group x diet interaction (P = 0.99). In contrast to our hypothesis, these results suggest that the deleterious effects of high sodium diets on cutaneous microvascular function are similar in normotensive salt sensitive and salt resistant individuals.

scholarly journals Minimal role for H1 and H2 histamine receptors in cutaneous thermal hyperemia to local heating in humans

2006 ◽  
Vol 100 (2) ◽  
pp. 535-540 ◽  
Author(s):  
Brett J. Wong ◽  
Sarah J. Williams ◽  
Christopher T. Minson
Keyword(s):  
Blood Flow ◽  
Receptor Antagonist ◽  
Skin Blood Flow ◽  
Local Heating ◽  
Histamine Receptor ◽  
Receptor Activation ◽  
Control Site ◽  
Doppler Flowmetry ◽  
Histamine Receptor Antagonist ◽  
And Control

The precise mechanism(s) underlying the thermal hyperemic response to local heating of human skin are not fully understood. The purpose of this study was to investigate a potential role for H1 and H2 histamine-receptor activation in this response. Two groups of six subjects participated in two separate protocols and were instrumented with three microdialysis fibers on the ventral forearm. In both protocols, sites were randomly assigned to receive one of three treatments. In protocol 1, sites received 1) 500 μM pyrilamine maleate (H1-receptor antagonist), 2) 10 mM l-NAME to inhibit nitric oxide synthase, and 3) 500 μM pyrilamine with 10 mM NG-nitro-l-arginine methyl ester (l-NAME). In protocol 2, sites received 1) 2 mM cimetidine (H2 antagonist), 2) 10 mM l-NAME, and 3) 2 mM cimetidine with 10 mM l-NAME. A fourth site served as a control site (no microdialysis fiber). Skin sites were locally heated from a baseline of 33 to 42°C at a rate of 0.5°C/5 s, and skin blood flow was monitored using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated as LDF/mean arterial pressure. To normalize skin blood flow to maximal vasodilation, microdialysis sites were perfused with 28 mM sodium nitroprusside, and control sites were heated to 43°C. In both H1 and H2 antagonist studies, no differences in initial peak or secondary plateau phase were observed between control and histamine-receptor antagonist only sites or between l-NAME and l-NAME with histamine receptor antagonist. There were no differences in nadir response between l-NAME and l-NAME with histamine-receptor antagonist. However, the nadir response in H1 antagonist sites was significantly reduced compared with control sites, but there was no effect of H2 antagonist on the nadir response. These data suggest only a modest role for H1-receptor activation in the cutaneous response to local heating as evidenced by a diminished nadir response and no role for H2-receptor activation.

scholarly journals Blunted increases in skin sympathetic nerve activity are related to attenuated reflex vasodilation in aged human skin

2016 ◽  
Vol 121 (6) ◽  
pp. 1354-1362 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Jody L. Greaney ◽  
Lacy M. Alexander ◽  
W. Larry Kenney
Keyword(s):  
Older Adults ◽  
Sympathetic Nerve Activity ◽  
Local Heating ◽  
Doppler Flowmetry ◽  
Healthy Older Adults ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Dorsum Of Foot ◽  
Reflex Cutaneous Vasodilation ◽  
Cutaneous Vascular Conductance

Reflex cutaneous vasodilation in response to passive heating is attenuated in human aging. This diminished response is mediated, in part, by age-associated reductions in endothelial function; however, the contribution of altered skin sympathetic nervous system activity (SSNA) is unknown. We hypothesized that 1) healthy older adults would demonstrate blunted SSNA responses to increased core temperature compared with young adults and 2) the decreased SSNA response would be associated with attenuated cutaneous vasodilation. Reflex vasodilation was elicited in 13 young [23 ± 1 (SE) yr] and 13 older (67 ± 2 yr) adults using a water-perfused suit to elevate esophageal temperature by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating, 43°C). Reflex vasodilation was attenuated in older adults ( P < 0.001). During heating, SSNA increased in both groups ( P < 0.05); however, the response was significantly blunted in older adults ( P = 0.01). The increase in SSNA during heating was linearly related to cutaneous vasodilation in both young ( R2 = 0.87 ± 0.02, P < 0.01) and older ( R2 = 0.76 ± 0.05, P < 0.01) adults; however, slope of the linear regression between ΔSSNA and ΔCVC was reduced in older compared with young (older: 0.05 ± 0.01 vs. young: 0.08 ± 0.01; P < 0.05). These data demonstrate that age-related impairments in reflex cutaneous vasodilation are mediated, in part, by blunted efferent SSNA during hyperthermia.

Sensory nerves and nitric oxide contribute to reflex cutaneous vasodilation in humans

2013 ◽  
Vol 304 (8) ◽  
pp. R651-R656 ◽  
Author(s):  
Brett J. Wong
Keyword(s):  
Nitric Oxide ◽  
Heat Stress ◽  
Core Temperature ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Whole Body ◽  
Oral Temperature ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Reflex Cutaneous Vasodilation

We tested the hypothesis that inhibition of cutaneous sensory nerves would attenuate reflex cutaneous vasodilation in response to an increase in core temperature. Nine subjects were equipped with four microdialysis fibers on the forearm. Two sites were treated with topical anesthetic EMLA cream for 120 min. Sensory nerve inhibition was verified by lack of sensation to a pinprick. Microdialysis fibers were randomly assigned as 1) lactated Ringer (control); 2) 10 mM nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase; 3) EMLA + lactated Ringer; and 4) EMLA + l-NAME. Laser-Doppler flowmetry was used as an index of skin blood flow, and blood pressure was measured via brachial auscultation. Subjects wore a water-perfused suit, and oral temperature was monitored as an index of core temperature. The suit was perfused with 50°C water to initiate whole body heat stress to raise oral temperature 0.8°C above baseline. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). There was no difference in CVC between control and EMLA sites (67 ± 5 vs. 69 ± 6% CVCmax), but the onset of vasodilation was delayed at EMLA compared with control sites. The l-NAME site was significantly attenuated compared with control and EMLA sites (45 ± 5% CVCmax; P < 0.01). Combined EMLA + l-NAME site (25 ± 6% CVCmax) was attenuated compared with control and EMLA ( P < 0.001) and l-NAME only ( P < 0.01). These data suggest cutaneous sensory nerves contribute to reflex cutaneous vasodilation during the early, but not latter, stages of heat stress, and full expression of reflex cutaneous vasodilation requires functional sensory nerves and NOS.

scholarly journals Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids

2013 ◽  
Vol 304 (5) ◽  
pp. H667-H673 ◽  
Author(s):  
Naoto Fujii ◽  
Maggie C. Reinke ◽  
Vienna E. Brunt ◽  
Christopher T. Minson
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Local Heating ◽  
Area Under The Curve ◽  
Daily Consumption ◽  
Cutaneous Vasodilation ◽  
Cox Inhibitor ◽  
Young Smokers ◽  
Synthase Inhibitor

Cigarette smoking attenuates acetylcholine (ACh)-induced cutaneous vasodilation in humans, but the underlying mechanisms are unknown. We tested the hypothesis that smokers have impaired nitric oxide (NO)- and cyclooxygenase (COX)-dependent cutaneous vasodilation to ACh infusion. Twelve young smokers, who have smoked more than 5.2 ± 0.7 yr with an average daily consumption of 11.4 ± 1.2 cigarettes, and 12 nonsmokers were tested. Age, body mass index, and resting mean arterial pressure were similar between the groups. Cutaneous vascular conductance (CVC) was evaluated as laser-Doppler flux divided by mean arterial pressure, normalized to maximal CVC (local heating to 43.0°C plus sodium nitroprusside administration). We evaluated the increase in CVC from baseline to peak (CVCΔpeak) and area under the curve of CVC (CVCAUC) during a bolus infusion (1 min) of 137.5 μM ACh at four intradermal microdialysis sites: 1) Ringer (control), 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combination of l-NAME + ketorolac. CVCΔpeakand CVCAUCat the Ringer site in nonsmokers were greater than in smokers (CVCΔpeak, 42.9 ± 5.1 vs. 22.3 ± 3.5%max, P < 0.05; and CVCAUC, 8,085 ± 1,055 vs. 3,145 ± 539%max·s, P < 0.05). In nonsmokers, CVCΔpeakand CVCAUCat the l-NAME site were lower than the Ringer site (CVCΔpeak, 29.5 ± 6.2%max, P < 0.05; and CVCAUC, 5,377 ± 1,109%max·s, P < 0.05), but in smokers, there were no differences between the Ringer and l-NAME sites (CVCΔpeak, 16.8 ± 4.3%max, P = 0.11; and CVCAUC, 2,679 ± 785%max·s, P = 0.30). CVCΔpeakand CVCAUCwere reduced with ketorolac in nonsmokers (CVCΔpeak, 13.3 ± 3.6%max, P < 0.05; and CVCAUC, 1,967 ± 527%max·s, P < 0.05) and smokers (CVCΔpeak, 7.8 ± 1.8%max, P < 0.05; and CVCAUC, 1,246 ± 305%max·s, P < 0.05) and at the combination site in nonsmokers (CVCΔpeak, 15.9 ± 3.1%max, P < 0.05; and CVCAUC, 2,660 ± 512%max·s, P < 0.05) and smokers (CVCΔpeak, 11.5 ± 2.6%max, P < 0.05; and CVCAUC, 1,693 ± 409%max·s, P < 0.05), but the magnitudes were greater in nonsmokers ( P < 0.05). These results suggest that impaired ACh-induced skin vasodilation in young smokers is related to diminished NO- and COX-dependent vasodilation.

Nitric oxide synthase inhibition does not alter the reactive hyperemic response in the cutaneous circulation

2003 ◽  
Vol 95 (2) ◽  
pp. 504-510 ◽  
Author(s):  
Brett J. Wong ◽  
Brad W. Wilkins ◽  
Lacy A. Holowatz ◽  
Christopher T. Minson
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Reactive Hyperemia ◽  
Area Under The Curve ◽  
Arterial Occlusion ◽  
Ringer Solution ◽  
Doppler Flowmetry ◽  
Forearm Skin ◽  
Cutaneous Circulation ◽  
Hyperemic Response

Reactive hyperemia is the sudden rise in blood flow after release of an arterial occlusion. Currently, the mechanisms mediating this response in the cutaneous circulation are poorly understood. The purpose of this study was to 1) characterize the reactive hyperemic response in the cutaneous circulation and 2) determine the contribution of nitric oxide (NO) to reactive hyperemia. Using laser-Doppler flowmetry, we characterized reactive hyperemia after 3-, 5-, 10-, and 15-min arterial occlusions in 10 subjects. The total hyperemic response was calculated by taking the area under the curve (AUC) of the hyperemic response minus baseline skin blood flow (SkBF) {i.e., total hyperemic response = AUC - [baseline SkBF as %maximal cutaneous vascular conductance (CVCmax) × duration of hyperemic response in s]}. For the characterization protocol, the total hyperemic response significantly increased as the period of ischemia increased from 5 to 15 min ( P < 0.05). However, the 3-min response was not significantly different from the 5-min response. In the NO contribution protocol, two microdialysis fibers were placed in the forearm skin of eight subjects. One site served as a control and was continuously perfused with Ringer solution. The second site was continuously perfused with 10 mM NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NO synthase. CVC was calculated as flux/mean arterial pressure and normalized to maximal blood flow (28 mM sodium nitroprusside). The total hyperemic response in control sites was not significantly different from l-NAME sites after a 5-min occlusion (3,261 ± 890 vs. 2,907 ± 531% CVCmax · s). Similarly, total hyperemic responses in control sites were not different from l-NAME sites (9,155 ± 1,121 vs. 9,126 ± 1,088%CVCmax · s) after a 15-min arterial occlusion. These data suggest that NO does not directly mediate reactive hyperemia and that NO is not produced in response to an increase in shear stress in the cutaneous circulation.

Decreased nitric oxide- and axon reflex-mediated cutaneous vasodilation with age during local heating

2002 ◽  
Vol 93 (5) ◽  
pp. 1644-1649 ◽  
Author(s):  
Christopher T. Minson ◽  
Lacy A. Holowatz ◽  
Brett J. Wong ◽  
W. Larry Kenney ◽  
Brad W. Wilkins
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
The Elderly ◽  
Axon Reflex ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Older Subjects ◽  
Initial Peak ◽  
Age Related Changes

Cutaneous vasodilation is reduced in healthy older vs. young subjects; however, the mechanisms that underlie these age-related changes are unclear. Our goal in the present study was to determine the role of nitric oxide (NO) and the axon reflexes in the skin blood flow (SkBF) response to local heating with advanced age. We placed two microdialysis fibers in the forearm skin of 10 young (Y; 22 ± 2 yr) and 10 older (O; 77 ± 5 yr) men and women. SkBF over each site was measured by laser-Doppler flowmetry (LDF; Moor DRT4). Both sites were heated to 42°C for ∼60 min while 10 mM N G-nitro-l-arginine methyl ester (l-NAME) was infused throughout the protocol to inhibit NO synthase (NOS) in one site and 10 mM l-NAME was infused after 40 min of local heating in the second site. Data were expressed as a percentage of maximal vasodilation (%CVCmax; 28 mM nitroprusside infusion). Local heating beforel-NAME infusion resulted in a significantly reduced initial peak (Y: 61 ± 2%CVCmax vs. O: 46 ± 4%CVCmax) and plateau (Y: 93 ± 2%CVCmaxvs. O: 82 ± 5%CVCmax) CVC values in older subjects ( P < 0.05). When NOS was inhibited after 40 min of heating, CVC declined to the same value in the young and older groups. Thus the overall contribution of NO to the plateau phase of the SkBF response to local heating was less in the older subjects. The initial peak response was significantly lower in the older subjects in both microdialysis sites (Y: 52 ± 4%CVCmax vs. O: 38 ± 5%CVCmax; P < 0.05). These data suggest that age-related changes in both axon reflex-mediated and NO-mediated vasodilation contribute to attenuated cutaneous vasodilator responses in the elderly.

scholarly journals Sex differences in the mechanisms mediating blunted cutaneous microvascular function in young black men and women

2018 ◽  
Vol 315 (4) ◽  
pp. H1063-H1071 ◽  
Author(s):  
Jordan C. Patik ◽  
Bryon M. Curtis ◽  
Aida Nasirian ◽  
Jennifer R. Vranish ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Sex Differences ◽  
Black Women ◽  
Black Men ◽  
Local Heating ◽  
Black Population ◽  
Control Site ◽  
Microvascular Function ◽  
Vascular Conductance ◽  
Men And Women ◽  
Cutaneous Vascular Conductance

The black population exhibits attenuated vasodilatory function across their lifespan, yet little is known regarding the mechanisms of this impairment. Recent evidence suggests a potential role for oxidative stress. Therefore, we tested the hypothesis that NADPH oxidase (NOX) and/or xanthine oxidase (XO) contribute to blunted nitric oxide (NO)-mediated cutaneous microvascular function in young black adults. In 30 white and black subjects (8 men and 7 women in each group), local heating was performed while NOX and XO were inhibited by apocynin and allopurinol, respectively, via intradermal microdialysis. The plateau in cutaneous vascular conductance (red blood cell flux/mean arterial pressure) during 39°C local heating at each site was compared with a control site perfused with lactated Ringer solution. Subsequent inhibition of NO synthase via Nω-nitro-l-arginine methyl ester allowed for quantification of the NO contribution to vasodilation during heating. Black individuals, relative to white individuals, had a blunted cutaneous vascular conductance plateau at the control site (45 ± 9 vs. 68 ± 13%max, P < 0.001) that was increased by both apocynin (61 ± 15%max, P < 0.001) and allopurinol (58 ± 17%max, P = 0.005). Black men and black women had similar responses to heating at the control site ( P = 0.99), yet apocynin and allopurinol increased this response only in black men (both P < 0.001 vs. control). The NO contribution was also increased via apocynin and allopurinol exclusively in black men. These findings suggest that cutaneous microvascular function is reduced because of NOX and XO activity in black men but not black women, identifying a novel sex difference in the mechanisms that contribute to blunted vascular responses in the black population. NEW & NOTEWORTHY We demonstrate that cutaneous microvascular responses to local heating are consistently reduced in otherwise healthy young black men and women relative to their white counterparts. Inhibition of NADPH oxidase and xanthine oxidase via apocynin and allopurinol, respectively, augments microvascular function in black men but not black women. These data reveal clear sex differences in the mechanisms underlying the racial disparity in cutaneous microvascular function.

Sign in / Sign up

Export Citation Format

Share Document