scholarly journals Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

2011 ◽  
Vol 301 (3) ◽  
pp. R763-R768 ◽  
Author(s):  
Lacy A. Holowatz ◽  
W. Larry Kenney
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Oxidant Stress ◽  
Microvascular Dysfunction ◽  
Local Skin ◽  
Cutaneous Vasodilation ◽  
Before And After ◽  
Atorvastatin Therapy ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ≪ngname≫ was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVCmax, P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVCmax, P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVCmax, P < 0.001) or combined with arginase inhibition (96 ± 3% CVCmax, P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVCmax, both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVCmax, P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVCmax, P > 0.05) or combined with arginase inhibition (67 ± 4% CVCmax, P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.

Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans

1998 ◽  
Vol 85 (3) ◽  
pp. 830-834 ◽  
Author(s):  
Shubha Shastry ◽  
Niki M. Dietz ◽  
John R. Halliwill ◽  
Ann S. Reed ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Potential Role ◽  
Contralateral Side ◽  
Laser Doppler ◽  
Cutaneous Vasodilation ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Blood

We sought to examine further the potential role of nitric oxide (NO) in the neurally mediated cutaneous vasodilation in nonacral skin during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured by using laser-Doppler flowmeters placed on both forearms. The NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) was given selectively to one forearm via a brachial artery catheter after marked cutaneous vasodilation had been established. During body heating, oral temperature increased by 1.1 ± 0.1°C while heart rate increased by 30 ± 6 beats/min. Mean arterial pressure stayed constant at 84 ± 2 mmHg. In the experimental forearm, cutaneous vascular conductance (CVC; laser-Doppler) decreased to 86 ± 5% of the peak response to heating ( P < 0.05 vs. pre-l-NMMA values) afterl-NMMA infusion. In some subjects, l-NMMA caused CVC to fall by ∼30%; in others, it had little impact on the cutaneous circulation. CVC in the control arm showed a similar increase with heating, then stayed constant whilel-NMMA was given to the contralateral side. These results demonstrate that NO contributes modestly, but not consistently, to cutaneous vasodilation during body heating in humans. They also indicate that NO is not the only factor responsible for the dilation.

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.

scholarly journals Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation

2016 ◽  
Vol 121 (3) ◽  
pp. 716-723 ◽  
Author(s):  
Vienna E. Brunt ◽  
Taylor M. Eymann ◽  
Michael A. Francisco ◽  
Matthew J. Howard ◽  
Christopher T. Minson
Keyword(s):  
Nitric Oxide ◽  
Water Immersion ◽  
Local Heating ◽  
Microvascular Function ◽  
Hot Water ◽  
Heat Therapy ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Doppler Flux ◽  
Cutaneous Vascular Conductance

Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38.5°C for 60 min/session; n = 9) or thermoneutral water immersion (sham, n = 9), and participated in experiments before and after the 8-wk intervention in which forearm cutaneous hyperemia to 39°C local heating was assessed at three microdialysis sites receiving 1) Lactated Ringer's (Control), 2) Nω-nitro-l-arginine (l-NNA; nonspecific NO synthase inhibitor), and 3) 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic. The arm used for microdialysis experiments remained out of the water at all times. Data are means ± SE cutaneous vascular conductance (CVC = laser Doppler flux/mean arterial pressure), presented as percent maximal CVC (% CVCmax). Heat therapy increased local heating plateau from 42 ± 6 to 53 ± 6% CVCmax ( P < 0.001) and increased NO-dependent dilation (difference in plateau between Control and l-NNA sites) from 26 ± 6 to 38 ± 4% CVCmax ( P < 0.01), while no changes were observed in the sham group. When data were pooled across all subjects at 0 wk, Tempol had no effect on the local heating response ( P = 0.53 vs. Control). There were no changes at the Tempol site across interventions ( P = 0.58). Passive heat therapy improves cutaneous microvascular function by improving NO-dependent dilation, which may have clinical implications.

scholarly journals Effect of elevated local temperature on cutaneous vasoconstrictor responsiveness in humans

2009 ◽  
Vol 106 (2) ◽  
pp. 571-575 ◽  
Author(s):  
Jonathan E. Wingo ◽  
David A. Low ◽  
David M. Keller ◽  
R. Matthew Brothers ◽  
Manabu Shibasaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Nonlinear Regression Analysis ◽  
Local Skin ◽  
Vasoconstrictor Response ◽  
Independent Mechanism ◽  
Presynaptic Release ◽  
Cutaneous Vascular Conductance ◽  
Cutaneous Vasoconstriction

Cutaneous vascular conductance (CVC) increases in response to local skin heating. Although attenuation of vasoconstrictor responsiveness due to local heating has been demonstrated, the mechanism(s) responsible for this attenuation remains unclear. Nitric oxide has been shown to at least partially contribute to this response, but other mechanisms also may be involved. The purpose of this study was to test the hypothesis that local heating diminishes cutaneous vasoconstrictor responsiveness through a nitric oxide-independent mechanism by altering postsynaptic reactivity to norepinephrine. A follow-up protocol tested the hypothesis that local heating attenuates the presynaptic release of neurotransmitters that cause vasoconstriction, also via non-nitric oxide mechanisms. In protocol I, CVC was assessed in eight subjects during administration of increasing doses of norepinephrine (via intradermal microdialysis) at adjacent sites separately heated to 34°C and 40°C. In protocol II, which was identical to, but separate from, protocol I, CVC was assessed in seven subjects during administration of increasing doses of tyramine, which causes release of neurotransmitters from adrenergic nerves. At each site for both protocols, nitric oxide synthesis was inhibited (via microdialysis administration of NG-nitro-l-arginine methyl ester) and flow was matched (via microdialysis administration of adenosine); therefore, temperature was the only variable that differed between the sites. For both protocols, nonlinear regression analysis revealed no difference ( P > 0.05) in the effective drug concentration causing 50% of the vasoconstrictor response. Minimum CVC [6.3 ± 2.0 and 9.0 ± 4.0% of peak CVC (mean ± SD) for protocol I and 19.3 ± 9.3 and 20.5 ± 11.9% of peak CVC for protocol II at 34°C and 40°C sites, respectively] was not different between sites. Independent of nitric oxide, local skin heating to 40°C does not attenuate adrenergically mediated cutaneous vasoconstriction through pre- or postsynaptic mechanisms.

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 Sex- and limb-specific differences in the nitric oxide-dependent cutaneous vasodilation in response to local heating

2014 ◽  
Vol 307 (7) ◽  
pp. R914-R919 ◽  
Author(s):  
Anna E. Stanhewicz ◽  
Jody L. Greaney ◽  
W. Larry Kenney ◽  
Lacy M. Alexander
Keyword(s):  
Nitric Oxide ◽  
Local Heating ◽  
Ringer Solution ◽  
No Synthase ◽  
Site Assessment ◽  
Cutaneous Vasodilation ◽  
Dependent Component ◽  
Doppler Flux ◽  
Cutaneous Vascular Conductance ◽  
Nnos Inhibition

Local heating of the skin is commonly used to assess cutaneous microvasculature function. Controversy exists as to whether there are limb or sex differences in the nitric oxide (NO)-dependent contribution to this vasodilation, as well as the NO synthase (NOS) isoform mediating the responses. We tested the hypotheses that 1) NO-dependent vasodilation would be greater in the calf compared with the forearm; 2) total NO-dependent dilation would not be different between sexes within limb; and 3) women would exhibit greater neuronal NOS (nNOS)-dependent vasodilation in the calf. Two microdialysis fibers were placed in the skin of the ventral forearm and the calf of 19 (10 male and 9 female) young (23 ± 1 yr) adults for the local delivery of Ringer solution (control) or 5 mM Nω-propyl-l-arginine (NPLA; nNOS inhibition). Vasodilation was induced by local heating (42°C) at each site, after which 20 mM NG-nitro-l-arginine methyl ester (l-NAME) was perfused for within-site assessment of NO-dependent vasodilation. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and normalized to maximum (28 mM sodium nitroprusside, 43°C). Total NO-dependent vasodilation in the calf was lower compared with the forearm in both sexes (Ringer: 42 ± 5 vs. 62 ± 4%; P < 0.05; NPLA: 37 ± 3 vs. 59 ± 5%; P < 0.05) and total NO-dependent vasodilation was lower in the forearm for women (Ringer: 52 ± 6 vs. 71 ± 4%; P < 0.05; NPLA: 47 ± 6 vs. 68 ± 5%; P < 0.05). NPLA did not affect total or NO-dependent vasodilation across limbs in either sex ( P > 0.05). These data suggest that the NO-dependent component of local heating-induced cutaneous vasodilation is lower in the calf compared with the forearm. Contrary to our original hypothesis, there was no contribution of nNOS to NO-dependent vasodilation in either limb during local heating.

The Effect on Health of Some Cardiovascular Risk Factors

2017 ◽  
Vol 68 (10) ◽  
pp. 2237-2242
Author(s):  
Germaine Savoiu Balint ◽  
Mihaiela Andoni ◽  
Ramona Amina Popovici ◽  
Laura Cristina Rusu ◽  
Ioana Citu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Reactivity ◽  
Vascular Wall ◽  
Dose Effect ◽  
Organ Bath ◽  
Before And After ◽  
Specific Receptors ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Relaxing Response

Arterial endothelium produces a large ramge of active factors which are indispensable for modulation of vasomotor tone and maintenance of vascular wall integrity. From these factors, nitric oxide (NO), wich is released by the endothelial cells as a response to acetylcholine or adenosine action on specific receptors, plays an important role.NO is the result of oxidation process of L-arginine into L-citrulline, under the action of endothelial nitric oxide synthase (NOSe), wich is activated by intracelluar Ca2+ - calmodulin complex . Our study, performed in isolated organ bath, analyzed vascular reactivity of 12 guinea pigs� thoracic aorta rings. After phenylephrine -PHE 10-5 mol/L precontraction, the dose-effect curves for acetylcoline � ACH, adenosine 5� phosphate - 5�ADP and sodium nitroprusside � SNP were determined, before and after incubation of preparation, for 1 hour, with 5% hydrosoluble cigarettes smoke extract (CSE). Statistic analysis, performed with the use of t pair test and ANOVA parametric test, showed that incubation of vascular preparation with 5% CSE has increased the contractile response to PHE 10-5 mol/L (p[0.05), has reduced the endothelium-dependent relaxing response to ATP 10-5 mol/L (p[0.001) and 5�ADP 10-5 molo/L (p[0.001), but has not significantly modified the endothelium-independent relaxing response to SNP 10-5 mol/L (p=0.05). As a conclusion, vascular rings incubation with 5% CSE induced a decrease of endothelium NO synthesis under the action of AXH and 5�ADP, but did not change the smooth muscle fiber respomse in the presence of NO released by SNP.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals Role of mitochondria-derived reactive oxygen species in microvascular dysfunction in chronic kidney disease

2018 ◽  
Vol 314 (3) ◽  
pp. F423-F429 ◽  
Author(s):  
Danielle L. Kirkman ◽  
Bryce J. Muth ◽  
Meghan G. Ramick ◽  
Raymond R. Townsend ◽  
David G. Edwards
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Local Heating ◽  
Reactive Oxygen ◽  
Microvascular Dysfunction ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Cutaneous Vasodilation

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Mitochondrial dysfunction secondary to CKD is a potential source of oxidative stress that may impair vascular function. This study sought to determine if mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in stage 3–5 CKD. Cutaneous vasodilation in response to local heating was assessed in 20 CKD patients [60 ± 13 yr; estimated glomerular filtration rate (eGFR) 46 ± 13 ml·kg−1·1.73 m−2] and 11 matched healthy participants (58 ± 2 yr; eGFR >90 ml·kg−1·1.73 m−2). Participants were instrumented with two microdialysis fibers for the delivery of 1) Ringer solution, and 2) the mitochondria- specific superoxide scavenger MitoTempo. Skin blood flow was measured via laser Doppler flowmetry during standardized local heating (42°C). Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum conductance achieved with sodium nitroprusside infusion at 43°C. Urinary isofuran/F2-isoprostane ratios were assessed by gas-chromatography mass spectroscopy. Isofuran-to-F2-isoprostane ratios were increased in CKD patients (3.08 ± 0.32 vs. 1.69 ± 0.12 arbitrary units; P < 0.01) indicative of mitochondria-derived oxidative stress. Cutaneous vasodilation was impaired in CKD compared with healthy controls (87 ± 1 vs. 92 ± 1%CVCmax; P < 0.01). Infusion of MitoTempo significantly increased the plateau phase CVC in CKD patients (CKD Ringer vs. CKD MitoTempo: 87 ± 1 vs. 93 ± 1%CVCmax; P < 0.01) to similar levels observed in healthy controls ( P = 0.9). These data provide in vivo evidence that mitochondria-derived reactive oxygen species contribute to microvascular dysfunction in CKD and suggest that mitochondrial dysfunction may be a potential therapeutic target to improve CKD-related vascular dysfunction.

scholarly journals The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans

2008 ◽  
Vol 105 (1) ◽  
pp. 233-240 ◽  
Author(s):  
Gary J. Hodges ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
John M. Johnson
Keyword(s):  
Nitric Oxide ◽  
Neuropeptide Y ◽  
Neurotransmitter Release ◽  
Local Heating ◽  
Axon Reflex ◽  
Laser Doppler Flow ◽  
Doppler Flow ◽  
Vasodilator Response ◽  
Oxide Synthase ◽  
Dependent Mechanism

Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40°C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS; and 4) combined bretylium + l-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation ( P < 0.05), which was not different among those sites ( P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) BIBP-3226 to antagonize Y1 receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred ( n = 4) or abolished it ( n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly ( P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.

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