The Vasodilatory Response of Skin Microcirculation to Local Heating is Subject to Desensitization
MERAL CIPLAK
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorANTOINE PASCHE
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorABIGAEL HEIM
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorCHRISTIAN HAEBERLI
Institut de Physiologie, Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorBERNARD WAEBER
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorLUCAS LIAUDET
Service de Médecine Intensive Adulte, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorCorresponding Author
FRANÇOIS FEIHL
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Address correspondence to Francçois Feihl, Division de Physiopathologie Clinique, BH19-317, Centre Hospitalier Universitaire Vaudois (CHUV), 1011. Lausanne, Suisse. E-mail: [email protected]Search for more papers by this authorROLF ENGELBERGER
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorMERAL CIPLAK
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorANTOINE PASCHE
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorABIGAEL HEIM
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorCHRISTIAN HAEBERLI
Institut de Physiologie, Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorBERNARD WAEBER
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorLUCAS LIAUDET
Service de Médecine Intensive Adulte, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorCorresponding Author
FRANÇOIS FEIHL
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Address correspondence to Francçois Feihl, Division de Physiopathologie Clinique, BH19-317, Centre Hospitalier Universitaire Vaudois (CHUV), 1011. Lausanne, Suisse. E-mail: [email protected]Search for more papers by this authorROLF ENGELBERGER
Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland
Search for more papers by this authorABSTRACT
Background: In humans, local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). Because the vascular effects of NO may be subject to desensitization, we examined whether a first local thermal stimulus would attenuate the hyperemic response to a second one applied later. Methods: Twelve healthy young men were studied. Skin blood flow (SkBF) was measured on forearm skin with laser Doppler imaging. Local thermal stimuli (temperature step from 34 to 41°C maintained for 30 minutes) were applied with temperature-controlled chambers. We also tested the influence of prior local heating on the vasodilation induced by sodium nitroprusside (SNP), a donor of NO. Results: On reheating the same spot after two hours, the response of SkBF (i.e., plateau SkBF at 30 minutes minus SkBF at 34°C) was lower than during the first stimulation (mean±SD 404±212 perfusion units [PU] vs. 635±100 PU; P<0.001). There was no such difference when reheating after four hours (654±153 vs. 645±103 PU; P=NS). Two, but not four, hours after local heating, the response of SkBF to SNP was reduced. Conclusion: The NO-dependent hyperemic response induced by local heating in human skin is subject to desensitization. At least one part of the mechanism implicated consists of a desensitization to the effects of NO itself.
REFERENCES
- 1 Arora, S, Smakowski, P, Frykberg, RG, Simeone, LR, Freeman, R, LoGerfo, FW, Veves, A. Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy. Diabetes Care 1998 21: 1339–1344.
- 2 Barcroft, H, Edholm, OG. The effect of temperature on blood flow and deep temperature in the human forearm. J Physiol (Lond) 1943 102: 5–20.
- 3 Boegli, Y, Gremion, G, Golay, S, Kubli, S, Liaudet, L, Leyvraz, PF, Waeber, B, Feihl, F. Endurance training enhances vasodilation induced by nitric oxide in human skin. J Invest Dermatol 2003 121: 1197–1204.
- 4 Charkoudian, N, Eisenach, JH, Atkinson, JL, Fealey, RD, Joyner, MJ. Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans. J Appl Physiol 2002 92: 685–690.
- 5 Cracowski, JL, Lorenzo, S, Minson, CT. Effects of local anaesthesia on subdermal needle insertion pain and subsequent tests of microvascular function in human. Eur J Pharmacol 2007 559: 150–154.
- 6 Cracowski, JL, Minson, CT, Salvat-Melis, M, Halliwill, JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 2006 27: 503–508.
- 7 Droog, EJ, Henricson, J, Nilsson, GE, Sjoberg, F. A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects. Microvasc Res 2004 67: 197–202.
- 8 Durand, S, Fromy, B, Bouye, P, Saumet, JL, Abraham, P. Vasodilatation in response to repeated anodal current application in the human skin relies on aspirin-sensitive mechanisms. J Physiol 2002 540: 261–269.
- 9 Freund, PR, Brengelmann, GL, Rowell, LB, Engrav, L, Heimbach, DM. Vasomotor control in healed grafted skin in humans. J Appl Physiol 1981 51: 168–171.
- 10 Garcia-Cardena, G, Fan, R, Shah, V, Sorrentino, R, Cirino, G, Papapetropoulos, A, Sessa, WC. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998 392: 821–824.
- 11 Golay, S, Haeberli, C, Delachaux, A, Liaudet, L, Kucera, P, Waeber, B, Feihl, F. Local heating of human skin causes hyperemia without mediation by muscarinic cholinergic receptors or prostanoids. J Appl Physiol 2004 97: 1781–1786.
- 12 Gooding, KM, Hannemann, MM, Tooke, JE, Clough, GF, Shore, AC. Maximum skin hyperaemia induced by local heating: possible mechanisms. J Vasc Res 2006 43: 270–277.
- 13 Kellogg, DL Jr. In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. J Appl Physiol 2006 100: 1709–1718.
- 14 Kellogg, DL, Liu, Y, Kosiba, IF, O'Donnell, D. Role of nitric oxide in the vascular effects of local warming of the skin in humans. J Appl Physiol 1999 86: 1185–1190.
- 15 Kellogg, DL Jr, Zhao, JL, Wu, Y. Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo. Am J Physiol 2008 295: H123–H129.
- 16 Kellogg, DL Jr, Zhao, JL, Wu, Y. Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo. J Physiol (Lond) 2008 586: 847–857.
- 17 Kruger, A, Stewart, J, Sahityani, R, O'Riordan, E, Thompson, C, Adler, S, Garrick, R, Vallance, P, Goligorsky, MS. Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk. Kidney Int 2006 70: 157–164.
- 18 Kubli, S, Waeber, B, Dalle-Ave, A, Feihl, F. Reproducibility of laser Doppler imaging of skin blood flow as a tool to assess endothelial function. J Cardiovasc Pharmacol 2000 36: 640–648.
- 19 Magerl, W, Treede, RD. Heat-evoked vasodilatation in human hairy skin: axon reflexes due to low-level activity of nociceptive afferents. J Physiol 1996 497: 837–848.
- 20 Medow, MS, Minson, CT, Stewart, JM. Decreased microvascular nitric oxide–dependent vasodilation in postural tachycardia syndrome. Circulation 2005 112: 2611–2618.
- 21 Miller, OI, Tang, SF, Keech, A, Celermajer, DS. Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide. Lancet 1995 346: 51–52.
- 22 Minson, CT, Berry, LT, Joyner, MJ. Nitric oxide and neurally mediated regulation of skin blood flow during local heating. J Appl Physiol 2001 91: 1619–1626.
- 23 Pacher, P, Beckman, JS, Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007 87: 315–424.
- 24 Papapetropoulos, A, Zhou, Z, Gerassimou, C, Yetik, G, Venema, RC, Roussos, C, Sessa, WC, Catravas, JD. Interaction between the 90-kDa heat shock protein and soluble guanylyl cyclase: physiological significance and mapping of the domains mediating binding. Mol Pharmacol 2005 68: 1133–1141.
- 25 Pergola, PE, Kellogg, DL Jr, Johnson, JM, Kosiba, WA, Solomon, DE. Role of sympathetic nerves in the vascular effects of local temperature in human forearm skin. Am J Physiol 1993 265: H785–H792.
- 26 Ravichandran, LV, Johns, RA, Rengasamy, A. Direct and reversible inhibition of endothelial nitric oxide synthase by nitric oxide. Am J Physiol 1995 268: H2216–H2223.
- 27 Salvat-Melis, M, Carpentier, PH, Minson, CT, Boignard, A, McCord, GR, Paris, A, Moreau-Gaudry, A, Cracowski, JL. Digital thermal hyperaemia impairment does not relate to skin fibrosis or macrovascular disease in systemic sclerosis. Rheumatology (Oxford) 2006 45: 1490–1496.
- 28 Shastry, S, Joyner, MJ. Geldanamycin attenuates NO-mediated dilation in human skin. Am J Physiol 2002 282: H232–H236.
- 29 Shastry, S, Dietz, NM, Halliwill, JR, Reed, AS, Joyner, MJ. Effects of nitric oxide synthase inhibition on cutaneous vasodilation during body heating in humans. J Appl Physiol 1998 85: 830–834.
- 30 Sheehy, AM, Burson, MA, Black, SM. Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am J Physiol 1998 274: L833–L841.
- 31 Sokolnicki, LA, Roberts, SK, Wilkins, BW, Basu, A, Charkoudian, N. Contribution of nitric oxide to cutaneous microvascular dilation in individuals with type 2 diabetes mellitus. Am J Physiol 2007 292: E314–E318.
- 32 Stewart, JM, Medow, MS, Minson, CT, Taneja, I. Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome. Am J Physiol 2007 293: H2161–H2167.
- 33 Stewart, JM, Taneja, I, Glover, J, Medow, MS. Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome. Am J Physiol 2008 294: H466–H473.
- 34 Veves, A, Akbari, CM, Primavera, J, Donaghue, VM, Zacharoulis, D, Chrzan, JS, DeGirolami, U, LoGerfo, FW, Freeman, R. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes 1998 47: 457–463.
- 35 Vogel, RA, Corretti, MC, Plotnick, GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol 1997 79: 350–354.
- 36 Wardell, K, Naver, NK, Nilsson, GE, Wallin, BG. The cutaneous vascular axon reflex in humans characterized by laser Doppler perfusion imaging. J Physiol (Lond) 1993 460: 185–199.
- 37 Winer, BJ. Statistical Principles in Experimental Design 3rd ed. McGraw-Hill. New York 1971.
- 38 Yetik-Anacak, G, Xia, T, Dimitropoulou, C, Venema, RC, Catravas, JD. Effects of hsp90 binding inhibitors on sGC-mediated vascular relaxation. Am J Physiol Heart Circ Physiol 2006 291: H260–H268.