Acetylcholine‐Induced Vasodilation and Reactive Hyperemia Are Not Affected by Acute Cyclo‐Oxygenase Inhibition in Human Skin

Dalle-Ave, Anne; Kubli, Sandrine; Golay, Sandrine; Delachaux, A; Liaudet, Lucas; Waeber, Bernard; Feihl, François

doi:10.1080/10739680490449268

Cited by 30 publications

(37 citation statements)

References 32 publications

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“…These results contrast with those of Dalle-Ave et al (12) who found that neither cutaneous RH nor the cutaneous hyperemic response to acetylcholine depended on PGs. Results also contrast with those of Binggeli et al (3) who found that aspirin reduced rather than increased RH flow.…”

Section: Comparison With the Literaturecontrasting

confidence: 99%

“…For example, Wong et al (35) have shown that the duration of the falloff in flow of the cutaneous circulation is independent of NO synthase (NOS) inhibition, whereas Zhao et al (38) provided data that NO concentration measured by amperometric electrode did not change during RH. Also, the role of PGs in RH has been controversial (12,20). 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.…”

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confidence: 99%

“…Also, the role of PGs in RH has been controversial (12,20). 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, Dalle-Ave et al (12) 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).…”

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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 Literaturecontrasting

confidence: 99%

mentioning

confidence: 99%

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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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“…Even more debatable remains the role of prostaglandins in the ACh-mediated response in human skin microcirculation. While some studies have confirmed their role (Durand et al, 2004;Holowatz et al, 2005, Kellogg et al, 2005Khan, 1997;Noon et al, 1998), others failed to do so (Abou-Elenin et al, 2002;Dalle-Ave et al, 2004;Morris& Shore, 1996).…”

Section: Human Skin Microcirculation and The Endothelium: Impact Of Nmentioning

confidence: 99%

Assessment of Human Skin Microcirculation and Its Endothelial Function Using Laser Doppler Flowmetry

Lenasi¹

2011

Medical Imaging

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“…Most studies using laser Doppler method in skin microcirculation attempt to determine the contribution of either NO or prostaglandins to the regulation of vascular tone and the results are inconsistent (Warren 1994;Noon et al 1998;BerghoV et al 2002;Dalle-Ave et al 2004).…”

Section: Introductionmentioning

confidence: 98%

The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity

Lenasi

Štrucl

2008

Eur J Appl Physiol

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The role of nitric oxide (NO)- and prostacyclin (PGI(2))-independent mechanism, potentially attributable to endothelium-derived hyperpolarizing factor (EDHF), has not been extensively studied in human skin microcirculation. The aim of our study was to elucidate the contribution of the NO- and PGI(2)-independent mechanism to microvascular reactivity of cutaneous microcirculation. Skin perfusion was measured on the volar aspect of the forearm in 12 healthy male subjects (mean age 25.0 +/- 1.5), using laser Doppler (LD) fluxmetry. Combined endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX) inhibition was achieved by an intradermal injection (10 microl) of the eNOS inhibitor, L(omega)-monomethyl L-arginine (L-NMMA, 10 mM) and the COX inhibitor, diclofenac (10 mM); saline was injected as a control. LD flux was assessed at rest and after an iontophoretical application of acetylcholine (ACh, 1%), an endothelial agonist and sodium nitroprusside (SNP, 1%), an endothelium-independent agonist, respectively. Combined eNOS and COX inhibition had no effect on the baseline LDF (12.5 +/- 2.3 PU (perfusion units) in control vs. 10.9 +/- 1.8 PU in the treated site). On the other hand, the ACh-stimulated increase in LDF was significantly attenuated after eNOS and COX inhibition (390.5 +/- 43.5%), compared to the control (643.7 +/- 80.3% increase, t-test, P < 0.05). Nevertheless, at least 60% of ACh-mediated vasodilatation was preserved after combined eNOS and COX inhibition. eNOS and COX inhibition had no impact on the SNP-stimulated increase in LDF (768.8 +/- 70.5% in control vs. 733.5 +/- 54.6% in the treated site). These findings indicate that NO- and PGI(2)-independent mechanism plays an important role in the regulation of blood flow in the human skin microcirculation.

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Acetylcholine‐Induced Vasodilation and Reactive Hyperemia Are Not Affected by Acute Cyclo‐Oxygenase Inhibition in Human Skin

Abstract: These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism.

Cited by 30 publications

References 32 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

Assessment of Human Skin Microcirculation and Its Endothelial Function Using Laser Doppler Flowmetry

The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity

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