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

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Abstract

The role of nitric oxide (NO)- and prostacyclin (PGI2)-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 PGI2-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 μl) of the eNOS inhibitor, Lω-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 PGI2-independent mechanism plays an important role in the regulation of blood flow in the human skin microcirculation.

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Acknowledgments

We would like to thank to the volunteers for participating in the study. The study was funded by the Slovenian Research Agency, Grant J3-6109.

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  1. Institute of Physiology, School of Medicine, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia

    Helena Lenasi & Martin Štrucl

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  1. Helena Lenasi
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  2. Martin Štrucl
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Correspondence to Helena Lenasi.

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Lenasi, H., Štrucl, M. The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity. Eur J Appl Physiol 103, 719–726 (2008). https://doi.org/10.1007/s00421-008-0769-8

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