scholarly journals The nitric oxide dependence of cutaneous microvascular function to independent and combined hypoxic cold exposure

2020 ◽  
Vol 129 (4) ◽  
pp. 947-956
Author(s):  
Josh T. Arnold ◽  
Alex B. Lloyd ◽  
Stephen J. Bailey ◽  
Tomomi Fujimoto ◽  
Ryoko Matsutake ◽  
...  

When separated from local cooling, whole body cooling elicited cutaneous reflex vasoconstriction via mechanisms independent of nitric oxide removal. Hypoxia elicited cutaneous vasodilatation via mechanisms mediated primarily by nitric oxide synthase, rather than xanthine oxidase-mediated nitrite reduction. Cold-induced vasoconstriction was blunted by the opposing effect of hypoxic vasodilatation, whereas the underpinning mechanisms did not interrelate in the absence of local cooling. Full vasoconstriction was restored with nitric oxide synthase inhibition.

1997 ◽  
Vol 93 (2) ◽  
pp. 175-179 ◽  
Author(s):  
Jerzy Leppert ◽  
Åsa Ringqvist ◽  
Johan Ahlner ◽  
Urban Myrdal ◽  
Marie-Louise Walker-Engström ◽  
...  

1. Primary Raynaud's phenomenon (PRP) is characterized by increased vasoconstrictor tone that develops during exposure to cold. The symptoms are most pronounced during the winter months with low outdoor temperature. The l-arginine—nitric oxide (NO)—cyclic GMP (cGMP) pathway plays an important role in counteracting vasospasm. The aim of the present study was to investigate if the venous cGMP response to whole-body cooling in women with PRP varied with the season of the year. 2. The study was performed as an open parallel-group comparison between women with PRP and healthy female controls during the winter months of February 1994 and 1995 and in the summer month of August 1994. Blood samples were drawn just before and 40 min after whole-body cooling. 3. There were no significant changes in venous cGMP after whole-body cooling in women with PRP during the winter months of February 1994 and 1995. Cold exposure in the summer month of August resulted, however, in a significant increase in venous cGMP (P < 0.01). In contrast, the healthy women responded with a significant increase in venous cGMP on all three test occasions: February 1994 (P < 0.05), August 1994 (P < 0.05) and February 1995 (P < 0.01) 4. A seasonal variation in venous cGMP response to whole-body cooling was observed only in women with PRP. Healthy women responded to cold exposure with an increase in venous cGMP during summer and winter, whereas females with PRP showed an increase only during summer. Results from the present study might indicate seasonal variation in the regulation of constitutive nitric oxide synthetase in women with PRP, which may contribute to new therapeutic approaches.


2010 ◽  
Vol 109 (3) ◽  
pp. 768-777 ◽  
Author(s):  
William G. Schrage ◽  
Brad W. Wilkins ◽  
Christopher P. Johnson ◽  
John H. Eisenach ◽  
Jacqueline K. Limberg ◽  
...  

The vasodilator signals regulating muscle blood flow during exercise are unclear. We tested the hypothesis that in young adults leg muscle vasodilation during steady-state exercise would be reduced independently by sequential pharmacological inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) with NG-nitro-l-arginine methyl ester (l-NAME) and ketorolac, respectively. We tested a second hypothesis that NOS and COX inhibition would increase leg oxygen consumption (V̇o2) based on the reported inhibition of mitochondrial respiration by nitric oxide. In 13 young adults, we measured heart rate (ECG), blood pressure (femoral venous and arterial catheters), blood gases, and venous oxygen saturation (indwelling femoral venous oximeter) during prolonged (25 min) steady-state dynamic knee extension exercise (60 kick/min, 19 W). Leg blood flow (LBF) was determined by Doppler ultrasound of the femoral artery. Whole body V̇o2 was measured, and leg V̇o2 was calculated from blood gases and LBF. Resting intra-arterial infusions of acetylcholine (ACh) and nitroprusside (NTP) tested inhibitor efficacy. Leg vascular conductance (LVC) to ACh was reduced up to 53 ± 4% by l-NAME + ketorolac infusion, and the LVC responses to NTP were unaltered. Exercise increased LVC from 4 ± 1 to 33.1 ± 2 ml·min−1·mmHg−1 and tended to decrease after l-NAME infusion (31 ± 2 ml·min−1·mmHg−1, P = 0.09). With subsequent administration of ketorolac LVC decreased to 29.6 ± 2 ml·min−1·mmHg−1 ( P = 0.02; n = 9). While exercise continued, LVC returned to control values (33 ± 2 ml·min−1·mmHg−1) within 3 min, suggesting involvement of additional vasodilator mechanisms. In four additional subjects, LVC tended to decrease with l-NAME infusion alone ( P = 0.08) but did not demonstrate the transient recovery. Whole body and leg V̇o2 increased with exercise but were not altered by l-NAME or l-NAME + ketorolac. These data indicate a modest role for NOS- and COX-mediated vasodilation in the leg of exercising humans during prolonged steady-state exercise, which can be restored acutely. Furthermore, NOS and COX do not appear to influence muscle V̇o2 in untrained healthy young adults.


2007 ◽  
Vol 293 (5) ◽  
pp. H3187-H3192 ◽  
Author(s):  
Gary J. Hodges ◽  
Wojciech A. Kosiba ◽  
Kun Zhao ◽  
Guy E. Alvarez ◽  
John M. Johnson

Previous work showed that local cooling (LC) attenuates the vasoconstrictor response to whole body cooling (WBC). We tested the extent to which this attenuation was due to the decreased baseline skin blood flow following LC. In eight subjects, skin blood flow was assessed using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was expressed as LDF divided by blood pressure. Subjects were dressed in water-perfused suits to control WBC. Four forearm sites were prepared with microdialysis fibers, local heating/cooling probe holders, and laser-Doppler probes. Three sites were locally cooled from 34 to 28°C, reducing CVC to 45.9 ± 3.9, 42 ± 3.9, and 44.5 ± 4.8% of baseline ( P < 0.05 vs. baseline; P > 0.05 among sites). At two sites, CVC was restored to precooling baseline levels with sodium nitroprusside (SNP) or isoproterenol (Iso), increasing CVC to 106.4 ± 12.4 and 98.9 ± 10.1% of baseline, respectively ( P > 0.05 vs. precooling). Whole body skin temperature, apart from the area of blood flow measurement, was reduced from 34 to 31°C. Relative to the original baseline, CVC decreased ( P < 0.05) by 44.9 ± 2.8 (control), 11.3 ± 2.4 (LC only), 29 ± 3.7 (SNP), and 45.8 ± 8.7% (Iso). The reductions at LC only and SNP sites were less than at control or Iso sites ( P < 0.05); the responses at those latter sites were not different ( P > 0.05), suggesting that the baseline change in CVC with LC is important in the attenuation of reflex vasoconstrictor responses to WBC.


2021 ◽  
Vol 15 ◽  
Author(s):  
Edward C. Harding ◽  
Wei Ba ◽  
Reesha Zahir ◽  
Xiao Yu ◽  
Raquel Yustos ◽  
...  

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.


2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Hsi-Hsing Yang ◽  
Ching-Ping Chang ◽  
Juei-Tang Cheng ◽  
Mao-Tsun Lin

Whole body cooling is the current therapy of choice for heatstroke because the therapeutic agents are not available. In this study, we assessed the effects of whole body cooling on several indices of acute lung inflammation and injury which might occur during heatstroke. Anesthetized rats were randomized into the following groups and given (a) no treatment or (b) whole body cooling immediately after onset of heatstroke. As compared with the normothermic controls, the untreated heatstroke rats had higher levels of pleural exudates volume and polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric oxide synthase expression, histologic lung injury score, and bronchoalveolar proinflammatory cytokines and glutamate, andPaCO2. In contrast, the values of mean arterial pressure, heart rate,PaO2, pH, and bloodHCO3−were all significantly lower during heatstroke. The acute lung inflammation and injury and electrolyte imbalance that occurred during heatstroke were significantly reduced by whole body cooling. In conclusion, we identified heat-induced acute lung inflammation and injury and electrolyte imbalance could be ameliorated by whole body cooling.


Resuscitation ◽  
2007 ◽  
Vol 74 (3) ◽  
pp. 516-525 ◽  
Author(s):  
Jose A. Adams ◽  
Dongmei Wu ◽  
Jorge Bassuk ◽  
Jaqueline Arias ◽  
Hector Lozano ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1041
Author(s):  
Magdalena Wiecek ◽  
Zbigniew Szygula ◽  
Joanna Gradek ◽  
Justyna Kusmierczyk ◽  
Jadwiga Szymura

Aging causes oxidative stress, endothelial dysfunction and a reduction in the bioavailability of nitric oxide. The study aim was to determine whether, as a result of repeated whole-body exposure to cryogenic temperature (3 min −130 °C), there is an increase of inducible nitric oxide synthase (iNOS) concentration in senior subjects (59 ± 6 years), and if this effect is stronger in athletes. In 10 long-distance runners (RUN) and 10 untraining (UTR) men, 24 whole-body cryotherapy (WBC) procedures were performed. Prior to WBC, after 12th and 24th treatments and 7 days later, the concentration of iNOS, asymmetric dimethylarginine (ADMA), 3-nitrotyrosine (3-NTR), homocysteine (HCY), C-reactive protein (CRP) and interleukins such as: IL-6, IL-1β, IL-10 were measured. In the RUN and UTR groups, after 24 WBC, iNOS concentration was found to be comparable and significantly higher (F = 5.95, p < 0.01) (large clinical effect size) compared to before 1st WBC and after 12th WBC sessions. There were no changes in the concentration of the remaining markers as a result of WBC (p > 0.05). As a result of applying 24 WBC treatments, using the every-other-day model, iNOS concentration increased in the group of older men, regardless of their physical activity level. Along with this increase, there were no changes in nitro-oxidative stress or inflammation marker levels.


2010 ◽  
Vol 108 (2) ◽  
pp. 328-333 ◽  
Author(s):  
Fumio Yamazaki

Local cooling (LC) of nonglabrous skin causes vasoconstriction via the adrenergic and removal of nitric oxide (NO) systems. Since cooling increases reactive oxygen species in smooth muscle cells and induces increased sensitivity of α-adrenergic receptors, antioxidant supplementation may attenuate the vasoconstrictor response to skin LC via adrenergic and/or NO systems. To test this hypothesis, we examined the effects of acute l-ascorbate (Asc, 10 mM) supplementation in human skin on the vasoconstrictor responses to LC in skin with and without NO synthase (NOS) inhibition or adrenergic receptor blockade. In a three-part study, forearm sites were instrumented with microdialysis fibers, local coolers, and laser-Doppler flow (LDF) probes in healthy volunteers. Sites were cooled from 34 to 24°C at −1°C/min and maintained at 24°C for 20 min ( parts 1 and 2) or 30 min ( part 3). During the last 10 min of LC in parts 1 and 2, whole body cooling was performed to increase sympathetic vasoconstrictor activity. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure and expressed relative to the baseline value before cooling. Treatments in each part were as follows: part 1) untreated, Asc; part 2) NG-nitro-l-arginine methyl ester (l-NAME) to inhibit NOS, combined l-NAME + Asc; part 3) yohimbine (YOH) + propranolol (PRO) to antagonize α- and β-adrenergic receptors and combined YOH + PRO + Asc. CVC reduction during LC was smaller ( P < 0.001) at Asc sites (−31 ± 4%) than at untreated sites (−56 ± 5%). LC-induced reduction in CVC was smaller ( P < 0.05) at l-NAME + Asc sites (−23 ± 8%) than at l-NAME sites (−43 ± 7%). LC-induced reduction in CVC did not differ between at PRO + YOH sites (−56 ± 3%) and at PRO + YOH + Asc sites (−50 ± 3%). These findings suggest that antioxidant supplementation inhibits the vasoconstrictor response to direct cooling through an adrenoceptor-dependent mechanism in human skin.


2021 ◽  
Vol 327 ◽  
pp. 03003
Author(s):  
Atanas Vasilev ◽  
Radostina A. Angelova ◽  
Rositsa Velichkova

The use of an efficient personal cooling system in hot environments is becoming increasingly popular, as the increased air temperature provokes thermophysiological discomfort, heat stress, reduced productivity and could lead to several health issues. Different methods and devices for personal and local cooling have been developed over the years. The paper summarises the cooling methods applied in clothing and wearable items: phase-change materials, Peltier elements, evaporative cooling, water cooling and hybrid cooling. The local vs total (of the whole body) cooling is examined. The passive and active colling are analysed in terms of advantages, disadvantages and application.


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