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.

Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin

2003 ◽  
Vol 284 (5) ◽  
pp. H1662-H1667 ◽  
Author(s):  
Lacy A. Holowatz ◽  
Belinda L. Houghton ◽  
Brett J. Wong ◽  
Brad W. Wilkins ◽  
Aaron W. Harding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Core Temperature ◽  
The Elderly ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Forearm Skin ◽  
Vascular Responsiveness ◽  
Older Subjects ◽  
Young Subjects ◽  
Reflex Cutaneous Vasodilation

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 ± 2 yr) and seven older (71 ± 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N G-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0°C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 ± 6% maximal CVC (CVCmax) to 53 ± 3% CVCmax in the young subjects and from 64 ± 5% CVCmax to 29 ± 2% CVCmax in the older subjects with a 1.0°C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for ∼23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia ( P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.

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.

scholarly journals Acute dairy milk ingestion does not improve nitric oxide-dependent vasodilation in the cutaneous microcirculation

2016 ◽  
Vol 116 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Billie K. Alba ◽  
Anna E. Stanhewicz ◽  
W. Larry Kenney ◽  
Lacy M. Alexander
Keyword(s):  
Nitric Oxide ◽  
Epidemiological Studies ◽  
Protein Supplementation ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Cutaneous Microcirculation ◽  
Age Related ◽  
Milk Ingestion ◽  
Dairy Milk

AbstractIn epidemiological studies, chronic dairy milk consumption is associated with improved vascular health and reduced age-related increases in blood pressure. Although milk protein supplementation augments conduit artery flow-mediated dilation, whether or not acute dairy milk intake may improve microvascular function remains unclear. We hypothesised that dairy milk would increase direct measurement of endothelial nitric oxide (NO)-dependent cutaneous vasodilation in response to local skin heating. Eleven men and women (61 (sem2) years) ingested two or four servings (473 and 946 ml) of 1 % dairy milk or a rice beverage on each of 4 separate study days. In a subset of five subjects, an additional protocol was completed after 473 ml of water ingestion. Once a stable blood flow occurred, 15 mm-NG-nitro-l-arginine methyl ester was perfused (intradermal microdialysis) to quantify NO-dependent vasodilation. Red-blood-cell flux (RBF) was measured by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC=RBF/mean arterial pressure) was calculated and normalised to maximum (%CVCmax; 28 mm-sodium nitroprusside). Full expression of cutaneous vasodilation was not different among dairy milk, rice beverage and water, and there was no effect of serving size on the total vasodilatory response. Contrary to our hypothesis, NO-dependent vasodilation was lower for dairy milk than rice beverage (D: 49 (sem5), R: 55 (sem5) %CVCmax;P<0·01). Acute dairy milk ingestion does not augment NO-dependent vasodilation in the cutaneous microcirculation compared with a rice beverage control.

Preserved reflex cutaneous vasodilation in cystic fibrosis does not include an enhanced nitric oxide-dependent mechanism

2007 ◽  
Vol 102 (6) ◽  
pp. 2301-2306 ◽  
Author(s):  
Brad W. Wilkins ◽  
Elizabeth A. Martin ◽  
Shelly K. Roberts ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Blood Flow ◽  
Skin Blood Flow ◽  
Local Heating ◽  
No Synthase ◽  
Local Skin ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Reflex Cutaneous Vasodilation

In humans, vasoactive intestinal peptide (VIP) may play a role in reflex cutaneous vasodilation during body heating. We tested the hypothesis that the nitric oxide (NO)-dependent contribution to active vasodilation is enhanced in the skin of subjects with cystic fibrosis (CF), compensating for sparse levels of VIP. In 2 parallel protocols, microdialysis fibers were placed in the skin of 11 subjects with CF and 12 controls. Lactated Ringer was perfused at one microdialysis site and NG-nitro-l-arginine methyl ester (2.7 mg/ml) was perfused at a second microdialysis site. Skin blood flow was monitored over each site with laser-Doppler flowmetry. In protocol 1, local skin temperature was increased 0.5°C every 5 s to 42°C, and then it maintained at 42°C for ∼45 min. In protocol 2, subjects wore a tube-lined suit perfused with water at 50°C, sufficient to increase oral temperature (Tor) 0.8°C. Cutaneous vascular conductance (CVC) was calculated (flux/mean arterial pressure) and scaled as percent maximal CVC (sodium nitroprusside; 8.3 mg/ml). Vasodilation to local heating was similar between groups. The change (Δ%CVCmax) in CVC with NO synthase inhibition on the peak (9 ± 3 vs. 12 ± 5%CVCmax; P = 0.6) and the plateau (45 ± 3 vs. 35 ± 5%CVCmax; P = 0.1) phase of the skin blood flow response to local heating was similar in CF subjects and controls, respectively. Reflex cutaneous vasodilation increased CVC in CF subjects (58 ± 4%CVCmax) and controls (53 ± 4%CVCmax; P = 0.37) and NO synthase inhibition attenuated CVC in subjects with CF (37 ± 6%CVCmax) and controls (35 ± 5%CVCmax; P = 0.8) to a similar degree. Thus the preservation of cutaneous active vasodilation in subjects with CF is not associated with an enhanced NO-dependent vasodilation.

scholarly journals Acute ultraviolet radiation exposure attenuates nitric oxide-mediated vasodilation in the cutaneous microvasculature of healthy humans

2018 ◽  
Vol 125 (4) ◽  
pp. 1232-1237 ◽  
Author(s):  
S. Tony Wolf ◽  
Anna E. Stanhewicz ◽  
Nina G. Jablonski ◽  
W. Larry Kenney
Keyword(s):  
Nitric Oxide ◽  
Radiation Exposure ◽  
Local Heating ◽  
Skin Pigmentation ◽  
Ultraviolet B ◽  
Uvb Radiation ◽  
Doppler Flowmetry ◽  
Healthy Humans ◽  
Cutaneous Vasodilation ◽  
Uvb Exposure

5-Methyltetrahydrofolate (5-MTHF) is important for nitric oxide (NO)-mediated cutaneous microvascular vasodilation. Ultraviolet B (UVB) radiation may deplete 5-MTHF, either directly or via production of reactive oxygen species (ROS), decreasing NO-mediated vasodilation. We hypothesized that 1) acute UVB exposure would attenuate NO-dependent cutaneous vasodilation, 2) local perfusion of 5-MTHF or ascorbate (ASC) (antioxidant) would augment NO-dependent vasodilation after UVB, and 3) darker skin pigmentation would be UVB-protective. Intradermal microdialysis fibers ( n = 3) placed in each forearm of 22 healthy young adults (23 ± 1 yr; 8M/14F) locally delivered lactated Ringer’s (control), 5 mM 5-MTHF, or 10 mM ASC. One arm was UVB-exposed (300 mJ/cm2), and the other served as a nonexposed control (CON). Following UVB exposure, a standardized local heating (42°C) protocol induced cutaneous vasodilation. After attaining a plateau blood flow, 15 mM NG-nitro-l-arginine methyl ester (nitric oxide synthase inhibiter) was infused at all sites to quantify the NO contribution. Red cell flux was measured at each site by laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC = LDF/mean arterial pressure) was expressed as a percentage of maximum (28 mM sodium nitroprusside + 43°C). UVB attenuated NO-mediated vasodilation compared with CON (23.1 ± 3.6 vs. 33.9 ± 3.4%; P = 0.001). Delivery of 5-MTHF or ASC improved NO-mediated vasodilation versus lactated Ringer’s in the UVB-exposed arm (MTHF: 30.1 ± 4.8% vs. 23.1 ± 3.8%; P = 0.03; ASC: 30.9 ± 4.3% vs. 23.1 ± 3.8%; P = 0.02). Neither treatment affected the response in the nonexposed arm ( P ≥ 0.09). Skin pigmentation (melanin index) was not predictive of the UVB response ( P ≥ 0.34). These data suggest that acute UVB exposure attenuates NO-mediated vasodilation via direct and/or ROS-induced reductions in 5-MTHF, independent of skin pigmentation. NEW & NOTEWORTHY Endothelial-derived nitric oxide (NO) contributes to normal healthy function of the human cutaneous microvasculature. Bioavailability of 5-methyltetrahydrofolate (5-MTHF) is important for the production of NO. Ultraviolet (UV) radiation exposure, specifically UVB, may deplete cutaneous 5-MTHF, thereby reducing NO-mediated microvascular function. Our findings suggest that acute UVB exposure attenuates NO-mediated vasodilation of the cutaneous microvasculature via degradation of 5-MTHF. These findings advance our understanding of the potential negative health impacts of acute UV exposure.

scholarly journals Glycosaminoglycans in the Human Cornea: Age-Related Changes

2015 ◽  
Vol 7 ◽  
pp. OED.S17204 ◽  
Author(s):  
Elena Pacella ◽  
Fernanda Pacella ◽  
Giulio De Paolis ◽  
Francesca Romana Parisella ◽  
Paolo Turchetti ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
The Elderly ◽  
Human Cornea ◽  
Molecular Analyses ◽  
Age Related ◽  
Younger Age ◽  
Quantitative Results ◽  
Older Subjects ◽  
Male Subjects ◽  
Age Related Changes

Aim To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. Methods Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. Results The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. Discussion GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea.

scholarly journals ETBreceptor contribution to vascular dysfunction in postmenopausal women

2017 ◽  
Vol 313 (1) ◽  
pp. R51-R57 ◽  
Author(s):  
Megan M. Wenner ◽  
Kelly N. Sebzda ◽  
Andrew V. Kuczmarski ◽  
Ryan T. Pohlig ◽  
David G. Edwards
Keyword(s):  
Receptor Antagonist ◽  
Postmenopausal Women ◽  
Vascular Dysfunction ◽  
Local Heating ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Age Related ◽  
Measured Flow ◽  
Vasodilatory Function ◽  
Cutaneous Vascular Conductance

Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via the ETAreceptor. However, there are sex differences in the ET-1 system, and ETBreceptors are modulated by sex hormones. The purpose of this study was to test the hypothesis that ETBreceptors contribute to impaired vasodilatory function in postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating (42°C) via laser Doppler flowmetry in 18 young women (YW; 22 ± 1 yr) and 16 PMW (56 ± 1 yr). Cutaneous microdialysis perfusions of lactated Ringer (control), an ETBreceptor antagonist (BQ-788, 300 nM), and an ETAreceptor antagonist (BQ-123, 500 nM), were done through separate fibers, followed by perfusions of sodium nitroprusside (28 mM) and local heating to 43°C (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/mean arterial pressure and expressed as a percent of maximal dilation. FMD (YW: 7.5 ± 0.5 vs. PMW: 5.6 ± 0.6%) and cutaneous vasodilation (YW: 93 ± 2 vs. PMW: 83 ± 4%CVCmax) were lower in PMW (both P < 0.05). Blockade of ETBreceptors decreased cutaneous vasodilation in YW (87 ± 2%CVCmax; P < 0.05 vs. control) but increased vasodilation in PMW (93 ± 1%CVCmax; P < 0.05 vs. control). ETAreceptor blockade had minimal effect in YW (92 ± 1%CVCmax) but increased cutaneous vasodilation in PMW (91 ± 2%CVCmax; P < 0.05 vs. control). In conclusion, ETBreceptors mediate vasodilation in YW, but this effect is lost after menopause. Impaired vasodilatory function in PMW is due in part to a loss of ETB-mediated dilation.

Nitric oxide and neurally mediated regulation of skin blood flow during local heating

2001 ◽  
Vol 91 (4) ◽  
pp. 1619-1626 ◽  
Author(s):  
Christopher T. Minson ◽  
Latoya T. Berry ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Skin Blood Flow ◽  
Local Heating ◽  
Local Production ◽  
Axon Reflex ◽  
Secondary Progressive ◽  
Primary Finding ◽  
Initial Peak

The mechanisms underlying the skin blood flow (SkBF) response to local heating are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different interventions, including blockade of the axon reflex (EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (≥10 mM N G-nitro-l-arginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a percentage of maximal SkBF (SkBFmax; 50 mM sodium nitroprusside). At the initiation of local heating, SkBF rose to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial peak from 75+3 to 32 ± 2% SkBFmax ( P< 0.01 vs. control) but did not affect the plateau. NOS inhibition before and throughout local heating reduced the initial peak from 75 ± 3 to 56 ± 3% SkBFmax ( P< 0.01) and the plateau from 87 ± 4 to 40 ± 5%. NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone. Antebrachial nerve block did not affect the local heating SkBF response. The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO.

scholarly journals Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

AGE ◽  
2012 ◽  
Vol 35 (2) ◽  
pp. 331-342 ◽  
Author(s):  
Elisa Mitiko Kawamoto ◽  
Andrea Rodrigues Vasconcelos ◽  
Sabrina Degaspari ◽  
Ana Elisa Böhmer ◽  
Cristoforo Scavone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Cyclic Gmp ◽  
Oxidative Status ◽  
Age Related ◽  
Age Related Changes
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