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

Shastry, Shubha; Dietz, Niki M.; Halliwill, John R.; Reed, Ann S.; Joyner, Michael J.

doi:10.1152/jappl.1998.85.3.830

Cited by 151 publications

(162 citation statements)

References 22 publications

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“…Results also contrast with those of Binggeli et al (3) who found that aspirin reduced rather than increased RH flow. Some of the differences of our study from these other studies may be due to our use of locally delivered Keto versus the use of systemically administered PG inhibitors in the other studies (28,29). Systemic administration may exert potential generalized effects indirectly affecting peripheral blood flow.…”

Section: Comparison With the Literaturementioning

confidence: 85%

“…Thus whereas Larkin and Williams (20) studying laser-Doppler measurements of skin blood flow showed that RH in the human forearm is mediated by a local reflex involving sensory nerves and a cyclooxygenase (COX) product, showed that there was no significant response to acute systemic COX inhibitors. However, the systemic administration of drugs does not always produce an adequate blockade in the skin (28,29).NO, NOS isoforms, and COX products mutually interact since there is increasing evidence suggesting considerable "cross talk" between NO and PG biosynthetic pathways involving an active back modulation operated by reaction end products, including NO, PGs, and cyclic nucleotides (22). For example, thromboxane A 2 exerts inhibitory effects on bioavailable NO through increasing oxidative stress (32) and inhibiting NOS (36).…”

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confidence: 99%

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Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

Medow

Taneja²,

Stewart³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Medow MS, Taneja I, Stewart JM. Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol 293: H425-H432, 2007. First published March 16, 2007; doi:10.1152/ajpheart.01217.2006.-We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19 -25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC) or as the maximum %CVC (%CVCmax) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-L-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA ϩ Keto, and NLA ϩ sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a ␤-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 Ϯ 5 to 77 Ϯ 7%CVCmax, time to peak flow increased from 17 Ϯ 3 to 56 Ϯ 24 s, the area under the reactive hyperemic curve increased from 1,417 Ϯ 326 to 3,376 Ϯ 876%CVCmax ⅐ s, and the time constant for the decay of peak flow increased from 100 Ϯ 23 to 821 Ϯ 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA ϩ SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation. microdialysis; prostaglandin; skin REACTIVE HYPEREMIA (RH) is the sudden rise in muscle and skin blood flow that can be measured after release of ischemic arterial occlusion. It has been used as a clinical tool to evaluate both micro-and macrovascular function in normal subjects, as well as those with various disease states (11,31,33,34). Following release of the occlusion, postischemic vasodilation occurs in most tissues (30), but the precise vasodilatory response differs from one vascular bed to another. RH has been studied most often in skeletal muscle vasculature where it is currently thought that hyperemia is due to a combination of the myogenic response (4) and local vasoactive tissue-related substances, notably prostaglandins (PGs). Other factors that appear to strongly relate to the peak flow of the hyperemic response are the local concentration of potassium (17), nitric oxide (NO) (24), adenosine (9), and endothelium-dependent hyperpolarizing factor (EDHF) (37), which have been proposed as potential mediators for the excess cumulative blood flow, i.e., the total amount of bloo...

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Section: Comparison With the Literaturementioning

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

Medow

Taneja²,

Stewart³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…It has been shown that production, release, and vascular responsiveness to nitric oxide is abnormal in patients with CHF, [37][38][39][40] whereas studies have shown that Ϸ30% of the elevation in cutaneous vascular conductance during indirect whole-body heating is mediated by nitric oxide-dependent mechanisms. 41,42 Therefore, if nitric oxide production, release, and/or responsiveness are similarly attenuated in the skin of patients with CHF, this could explain a component of the observed reduction in cutaneous vasodilation during the whole-body heat stress.…”

Section: Cui Et Al Thermal Regulatory Responses In Chf 2289mentioning

confidence: 99%

Effects of Heat Stress on Thermoregulatory Responses in Congestive Heart Failure Patients

et al. 2005

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Background-Clinical observations suggest that tolerance to heat stress may be impaired in patients with cardiovascular diseases, particularly those associated with impaired ventricular function and congestive heart failure (CHF). However, thermoregulatory function during a controlled heat stress challenge in patients with CHF has not been studied. Methods and Results-To test the hypothesis that thermoregulatory responses are attenuated in such patients, we assessed cutaneous vasodilation and sweat rate in patients with stable class II-III CHF and in matched healthy subjects during passive whole-body heating. Whole-body heating induced a similar increase in internal temperature (Ϸ0.85°C) in both groups. The sweating responses in patients with CHF were not significantly different from that in control subjects. In contrast, the elevation in forearm cutaneous vascular conductance in patients with CHF was reduced by nearly 50% relative to the control subjects (3.8Ϯ0.8 versus 6.9Ϯ1.0 mL/100 mL tissue per minute per 100 mm Hg, Pϭ0.04). Moreover, maximal cutaneous vasodilator capacity to direct local heating in patients with CHF was also significantly lower than in control subjects, suggesting that vascular remodeling may be limiting cutaneous vasodilation during hyperthermia. Conclusions-These observations suggest that patients with CHF exhibit attenuated cutaneous vasodilator responses to both whole-body and local heating, whereas sweating responses are preserved. Attenuated cutaneous vasodilation may be a potential mechanism for heat intolerance in patients with CHF.

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“…Physiological mechanisms contributing to the disproportionate temporal progression of sudomotor and vasomotor dysfunction with age remain unclear. Furthermore, despite attempts to identify a putative signaling pathway or cotransmitter relating the two responses, including speculation over VIP (40), bradykinin (4), and nitric oxide (33), a single mechanism has not yet been elucidated. The regional progression of age-related vasomotor and sudomotor dysfunction is not well characterized, with limited vasomotor data available and conflicting results of regional sudomotor adjustments.…”

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confidence: 99%

Nonuniform, age-related decrements in regional sweating and skin blood flow

Smith

Alexander

Kenney

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Smith CJ, Alexander LM, Kenney WL. Nonuniform, age-related decrements in regional sweating and skin blood flow. Am J Physiol Regul Integr Comp Physiol 305: R877-R885, 2013. First published August 7, 2013 doi:10.1152/ajpregu.00290.2013.-Aging is associated with attenuated thermoregulatory function that varies regionally over the body. Decrements in vasodilation and sweating are well documented with age, yet limited data are available concerning the regional relation between these responses. We aimed to examine age-related alterations in the relation between regional sweating (RSR) and skin blood flow (SkBF) to thermal and pharmacological stimuli. Four microdialysis fibers were inserted in the ventral forearm, abdomen, thigh, and lower back of eight healthy aged subjects (64 Ϯ 7 yr) and nine young (23 Ϯ 3 yr) during 1) ACh dose response (1 ϫ 10 Ϫ7 to 0.1 M, mean skin temperature 34°C) and 2) passive whole body heating to ⌬1°C rise in oral temperature (Tor). RSR and SkBF were measured over each microdialysis membrane using ventilated capsules and laser-Doppler flowmetry. Maximal SkBF was measured at the end of both protocols (50 mM SNP). Regional sweating thresholds and RSR were attenuated in aged vs. young at all sites (P Ͻ 0.0001) during whole body heating. Vasodilation thresholds were similar between groups (P Ͼ 0.05). Attenuated SkBF were observed at the arm and back in the aged, representing 56 and 82% of those in the young at these sites, respectively (0.5 ⌬Tor). During ACh perfusion, SkBF (P ϭ 0.137) and RSR were similar between groups (P ϭ 0.326). Together these findings suggest regional age-related decrements in heat-activated sweat gland function but not cholinergic sensitivity. Functional consequences of such thermoregulatory impairment include the compromised ability of older individuals to defend core temperature during heat exposure and a subsequently greater susceptibility to heat-related illness and injury.sweating; aging; laser-Doppler flowmetry; skin blood flow; sweating HUMAN AGING IS ASSOCIATED with altered thermoregulatory function during both passive and exercise-induced hyperthermia, including attenuated reflex cutaneous vasodilation (26) and eccrine sweating responses (3,18,24). A functional loss of active cholinergic vasodilation cotransmitter function and dysfunction of second-messenger pathways (i.e., nitric oxide bioavailability) (8,11,12,31) contribute to attenuated cutaneous vasodilatory responses to elevations in core temperature (T core ), hindering convective heat loss. An age-related decline in thermoregulatory sweating further compromises heat loss and increases thermal strain in warm ambient conditions and during exercise. Reduced evaporative heat loss from the skin surface results from a decline in thermoregulatory sweating, due to a decreased thermal sensitivity (32) and atrophy of the sweat glands (17, 19), producing a lower sweat output per gland (23,24,39).Regional variation in sweating and skin blood flow (SkBF) responses to passive heating are well documented (29); howev...

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

Cited by 151 publications

References 22 publications

Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

Effects of Heat Stress on Thermoregulatory Responses in Congestive Heart Failure Patients

Nonuniform, age-related decrements in regional sweating and skin blood flow

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