scholarly journals eNOS and nNOS contribution to reflex cutaneous vasodilation during dynamic exercise in humans

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Tanner C McNamara ◽  
Jeremy Keen ◽  
Grant H Simmons ◽  
Lacy A Holowatz ◽  
Brett J Wong
Keyword(s):  
Dynamic Exercise ◽  
Cutaneous Vasodilation ◽  
Reflex Cutaneous Vasodilation ◽  
Exercise In Humans

scholarly journals Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation in middle-aged humans

2009 ◽  
Vol 106 (2) ◽  
pp. 500-505 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Low Dose ◽  
Aspirin Therapy ◽  
Oral Temperature ◽  
Middle Aged ◽  
Doppler Flowmetry ◽  
Healthy Humans ◽  
Cutaneous Vasodilation ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Reflex Cutaneous Vasodilation

Full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase- (COX) and nitric oxide synthase- (NOS) dependent mechanisms. Low-dose aspirin therapy is widely prescribed to inhibit COX-1 in platelets for atherothrombotic prevention. We hypothesized that chronic COX inhibition with daily low-dose aspirin therapy (81 mg) would attenuate reflex vasodilation in healthy human skin. Two microdialysis fibers were placed in forearm skin of seven middle-aged (57 ± 3 yr), normotensive, healthy humans with no preexisting cardiovascular disease, taking daily low-dose aspirin therapy (aspirin: 81 mg), and seven unmedicated, healthy, age-matched control (no aspirin, 55 ± 3 yr) subjects, with one site serving as a control (Ringer) and the other NOS inhibited (NOS inhibited: 10 mM NG-nitro-l-arginine methyl ester). Red cell flux was measured over each site by laser-Doppler flowmetry, as reflex vasodilation was induced by increasing core temperature (oral temperature) 1.0°C using a water-perfused suit. Cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVCmax; 28 mM sodium nitroprusside). CVCmax was not affected by either aspirin or NOS inhibition. The plateau in cutaneous vasodilation during heating (change in oral temperature = 1.0°C) was significantly attenuated in the aspirin group (aspirin: 25 ± 3% CVCmax vs. no aspirin: 50 ± 7% CVCmax, P < 0.001 between groups). NOS inhibition significantly attenuated %CVCmax in both groups (aspirin: 17 ± 2% CVCmax, no aspirin: 23 ± 3% CVCmax; P < 0.001 vs. control), but this attenuation was less in the no-aspirin treatment group ( P < 0.001). This is the first observation that chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation through both COX- and NOS-dependent mechanisms.

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.

Increases in intramuscular pressure raise arterial blood pressure during dynamic exercise

2001 ◽  
Vol 91 (5) ◽  
pp. 2351-2358 ◽  
Author(s):  
K. M. Gallagher ◽  
P. J. Fadel ◽  
S. A. Smith ◽  
K. H. Norton ◽  
R. G. Querry ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arterial Blood Pressure ◽  
Dynamic Exercise ◽  
Positive Pressure ◽  
Intramuscular Pressure ◽  
Arterial Blood ◽  
Exercise In Humans ◽  
Cuff Occlusion

This investigation was designed to determine the role of intramuscular pressure-sensitive mechanoreceptors and chemically sensitive metaboreceptors in affecting the blood pressure response to dynamic exercise in humans. Sixteen subjects performed incremental (20 W/min) cycle exercise to fatigue under four conditions: control, exercise with thigh cuff occlusion of 90 Torr (Cuff occlusion), exercise with lower body positive pressure (LBPP) of 45 Torr, and a combination of thigh cuff occlusion and LBPP (combination). Indexes of central command (heart rate, oxygen uptake, ratings of perceived exertion, and electromyographic activity), cardiac output, stroke volume, and total peripheral resistance were not significantly different between the four conditions. Mechanical stimulation during LBPP and combination conditions resulted in significant elevations in intramuscular pressure and mean arterial pressure from control at rest and throughout the incremental exercise protocol ( P < 0.05). Conversely, there existed no significant changes in mean arterial pressure when the metaboreflex was stimulated by cuff occlusion. These findings suggest that under normal conditions the mechanoreflex is tonically active and is the primary mediator of exercise pressor reflex-induced alterations in arterial blood pressure during submaximal dynamic exercise in humans.

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 Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans

2010 ◽  
Vol 108 (6) ◽  
pp. 1575-1581 ◽  
Author(s):  
Lacy A. Holowatz ◽  
John D. Jennings ◽  
James A. Lang ◽  
W. Larry Kenney
Keyword(s):  
Blood Flow ◽  
Skin Blood Flow ◽  
Low Dose ◽  
Middle Aged ◽  
Cutaneous Vasodilation ◽  
Dose Aspirin ◽  
Receptor Inhibition ◽  
Low Dose Aspirin ◽  
Adp Receptor ◽  
Reflex Cutaneous Vasodilation

Chronic systemic platelet cyclooxygenase (COX) inhibition with low-dose aspirin [acetylsalicylic acid (ASA)] significantly attenuates reflex cutaneous vasodilation in middle-aged humans, whereas acute, localized, nonisoform-specific inhibition of vascular COX with intradermal administration of ketorolac does not alter skin blood flow during hyperthermia. Taken together, these data suggest that platelets may be involved in reflex cutaneous vasodilation, and this response is inhibited with systemic pharmacological platelet inhibition. We hypothesized that, similar to ASA, specific platelet ADP receptor inhibition with clopidogrel would attenuate reflex vasodilation in middle-aged skin. In a double-blind crossover design, 10 subjects (53 ± 2 yr) were instrumented with four microdialysis fibers for localized drug administration and heated to increase body core temperature [oral temperature (Tor)] 1°C during no systemic drug (ND), and after 7 days of systemic ASA (81 mg) and clopidogrel (75 mg) treatment. Skin blood flow (SkBF) was measured using laser-Doppler flowmetry over each site assigned as 1) control, 2) nitric oxide synthase inhibited (NOS-I; 10 mM NG-nitro-l-arginine methyl ester), 3) COX inhibited (COX-I; 10 mM ketorolac), and 4) NOS-I + COX-I. Data were normalized and presented as a percentage of maximal cutaneous vascular conductance (%CVCmax; 28 mM sodium nitroprusside + local heating to 43°C). During ND conditions, SkBF with change (Δ) in Tor = 1.0°C was 56 ± 3% CVCmax. Systemic low-dose ASA and clopidogrel both attenuated reflex vasodilation (ASA: 43 ± 3; clopidogrel: 32 ± 3% CVCmax; both P < 0.001). In all trials, localized COX-I did not alter SkBF during significant hyperthermia (ND: 56 ± 7; ASA: 43 ± 5; clopidogrel: 35 ± 5% CVCmax; all P > 0.05). NOS-I attenuated vasodilation in ND and ASA (ND: 28 ± 6; ASA: 25 ± 4% CVCmax; both P < 0.001), but not with clopidogrel (27 ± 4% CVCmax; P > 0.05). NOS-I + COX-I was not different compared with NOS-I alone in either systemic treatment condition. Both systemic ASA and clopidogrel reduced the time required to increase Tor 1°C (ND: 58 ± 3 vs. ASA: 45 ± 2; clopidogrel: 39 ± 2 min; both P < 0.001). ASA-induced COX and specific platelet ADP receptor inhibition attenuate reflex vasodilation, suggesting platelet involvement in reflex vasodilation through the release of vasodilating factors.

Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans

1997 ◽  
Vol 83 (4) ◽  
pp. 1383-1388 ◽  
Author(s):  
G. Rådegran
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Coefficient Of Variation ◽  
Knee Extensor ◽  
Dynamic Exercise ◽  
Artery Blood Flow ◽  
Ultrasound Doppler ◽  
Femoral Artery Blood Flow ◽  
Human Limb ◽  
Exercise In Humans

Rådegran, G. Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. J. Appl. Physiol.83(4): 1383–1388, 1997.—Ultrasound Doppler has been used to measure arterial inflow to a human limb during intermittent static contractions. The technique, however, has neither been thoroughly validated nor used during dynamic exercise. In this study, the inherent problems of the technique have been addressed, and the accuracy was improved by storing the velocity tracings continuously and calculating the flow in relation to the muscle contraction-relaxation phases. The femoral arterial diameter measurements were reproducible with a mean coefficient of variation within the subjects of 1.2 ± 0.2%. The diameter was the same whether the probe was fixed or repositioned at rest (10.8 ± 0.2 mm) or measured during dynamic exercise. The blood velocity was sampled over the width of the diameter and the parabolic velocity profile, since sampling in the center resulted in an overestimation by 22.6 ± 9.1% ( P< 0.02). The femoral arterial Doppler blood flow increased linearly ( r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 ⋅ load (W) + 1.446 l/min] and was correlated positively with simultaneous thermodilution venous outflow measurements ( r = 0.996, P < 0.001). The two techniques were linearly related (Doppler = thermodilution ⋅ 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient of variation of ∼6% for both methods.

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