Oral sapropterin acutely augments reflex vasodilation in aged human skin through nitric oxide-dependent mechanisms

Journal of Applied Physiology

Volumn 115, Issue 7, 2013, Pages 972-978

  Stanhewicz, Anna E ^a   Alexander, Lacy M ^a,b   Kenney, W Larry ^a  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b 113 Noll Laboratory   (United States)

Author keywords

Aging; BH4; Skin blood flow; Temperature regulation

Indexed keywords

5,6,7,8-TETRAHYDROBIOPTERIN; BIOPTERIN; DRUG DERIVATIVE; NITRIC OXIDE; TETRAHYDROBIOPTERIN;

AGED; AGING; ARTICLE; BH4; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; CUTANEOUS PARAMETERS; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; FEVER; HUMAN; MALE; METABOLISM; MICROVASCULATURE; PATHOPHYSIOLOGY; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; REFLEX; SKIN; SKIN BLOOD FLOW; THERMOREGULATION; VASODILATATION;

AGING; BH4; SKIN BLOOD FLOW; TEMPERATURE REGULATION;

AGED; BIOPTERIN; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; FEVER; HUMANS; MALE; MICROVESSELS; NITRIC OXIDE; REFLEX; SKIN; SKIN AGING; VASODILATION;

EID: 84885226016     PISSN: 87507587     EISSN: 15221601     Source Type: Journal    
DOI: 10.1152/japplphysiol.00481.2013     Document Type: Article

References (45)

1. Alexander LM, Kutz JL, Kenney WL. Tetrahydrobiopterin increases NO-dependent vasodilation in hypercholesterolemic human skin through eNOS-coupling mechanisms. Am J Physiol Regul Integr Comp Physiol 304: R164-R169, 2013.
2. Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res 43: 521-531, 1999.
3. Aoki K, Kondo N, Shibasaki M, Takano S, Katsuura T. Circadian variation in skin blood flow responses to passive heat stress. Physiol Behav 63: 1-5, 1997.
4. Bennett LA, Johnson JM, Stephens DP, Saad AR, Kellogg DL Jr. Evidence for a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous vasculature of humans. J Physiol 552: 223-232, 2003.
5. Cosentino F, Hurlimann D, Delli Gatti C, Chenevard R, Blau N, Alp NJ, Channon KM, Eto M, Lerch P, Enseleit F, Ruschitzka F, Volpe M, Luscher TF, Noll G. Chronic treatment with tetrahydrobiopterin reverses endothelial dysfunction and oxidative stress in hypercholesterolaemia. Heart 94: 487-492, 2008.
6. Delp MD, Behnke BJ, Spier SA, Wu G, Muller-Delp JM. Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles. J Physiol 586: 1161-1168, 2008.
7. Detry JM, Brengelmann GL, Rowell LB, Wyss C. Skin and muscle components of forearm blood flow in directly heated resting man. J Appl Physiol 32: 506-511, 1972.
8. Eskurza I, Monahan KD, Robinson JA, Seals DR. Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol 286: H1528-H1534, 2004.
9. Eskurza I, Monahan KD, Robinson JA, Seals DR. Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing. J Physiol 556: 315-324, 2004.
10. Eskurza I, Myerburgh LA, Kahn ZD, Seals DR. Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults. J Physiol 568: 1057-1065, 2005.
11. Feillet F, Clarke L, Meli C, Lipson M, Morris AA, Harmatz P, Mould DR, Green B, Dorenbaum A, Giovannini M, Foehr E; Sapropterin Research Group. Pharmacokinetics of sapropterin in patients with phenylketonuria. Clin Pharmacokinet 47: 817-825, 2008.
12. Fiege B, Ballhausen D, Kierat L, Leimbacher W, Goriounov D, Schircks B, Thony B, Blau N. Plasma tetrahydrobiopterin and its pharmacokinetic following oral administration. Mol Genet Metab 81: 45-51, 2004.
13. Grant RT, Holling HE. Further observations on the vascular responses of the human limb to body warming, evidence for sympathetic vasodilator nerves in the normal subject. Clin Sci 3: 273-285, 1938.
14. Hattori Y, Hattori S, Wang X, Satoh H, Nakanishi N, Kasai K. Oral administration of tetrahydrobiopterin slows the progression of atherosclerosis in apolipoprotein E-knockout mice. Arterioscler Thromb Vasc Biol 27: 865-870, 2007.
15. Higashi Y, Sasaki S, Nakagawa K, Kimura M, Noma K, Hara K, Jitsuiki D, Goto C, Oshima T, Chayama K, Yoshizumi M. Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production. Atherosclerosis 186: 390-395, 2006.
16. Hodges GJ, Chiu C, Kosiba WA, Zhao K, Johnson JM. The effect of microdialysis needle trauma on cutaneous vascular responses in humans. J Appl Physiol 106: 1112-1118, 2009.
17. Holowatz LA, Houghton BL, Wong BJ, Wilkins BW, Harding AW, Kenney WL, Minson CT. Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin. Am J Physiol Heart Circ Physiol 284: H1662-H1667, 2003.
18. Holowatz LA, Jennings JD, Lang JA, Kenney WL. Ketorolac alters blood flow during normothermia but not during hyperthermia in middleaged human skin. J Appl Physiol 107: 1121-1127, 2009.
19. Holowatz LA, Thompson CS, Kenney WL. Acute ascorbate supplementation alone or combined with arginase inhibition augments reflex cutaneous vasodilation in aged human skin. Am J Physiol Heart Circ Physiol 291: H2965-H2970, 2006.
20. Holowatz LA, Thompson CS, Kenney WL. L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin. J Physiol 574: 573-581, 2006.
21. Huang A, Vita JA, Venema RC, Keaney JF Jr. Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 275: 17399-17406, 2000.
22. Kellogg DL Jr, Crandall CG, Liu Y, Charkoudian N, Johnson JM. Nitric oxide and cutaneous active vasodilation during heat stress in humans. J Appl Physiol 85: 824-829, 1998.
23. Kellogg DL Jr, Pergola PE, Piest KL, Kosiba WA, Crandall CG, Grossmann M, Johnson JM. Cutaneous active vasodilation in humans is mediated by cholinergic nerve cotransmission. Circ Res 77: 1222-1228, 1995.
24. Kellogg DL Jr, Zhao JL, Wu Y. Roles of nitric oxide synthase isoforms in cutaneous vasodilation induced by local warming of the skin and whole body heat stress in humans. J Appl Physiol 107: 1438-1444, 2009.
25. Kenney WL, Morgan AL, Farquhar WB, Brooks EM, Pierzga JM, Derr JA. Decreased active vasodilator sensitivity in aged skin. Am J Physiol Heart Circ Physiol 272: H1609-H1614, 1997.
26. Kuzkaya N, Weissmann N, Harrison DG, Dikalov S. Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase. J Biol Chem 278: 22546-22554, 2003.
27. Lang JA, Holowatz LA, Kenney WL. Localized tyrosine or tetrahydrobiopterin supplementation corrects the age-related decline in cutaneous vasoconstriction. J Physiol 588: 1361-1368, 2010.
28. McCord GR, Cracowski JL, Minson CT. Prostanoids contribute to cutaneous active vasodilation in humans. Am J Physiol Regul Integr Comp Physiol 291: R596-R602, 2006.
29. Meininger CJ, Wu G. Regulation of endothelial cell proliferation by nitric oxide. Meth Enzymol 352: 280-295, 2002.
30. Milstien S, Katusic Z. Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Biochem Biophys Res Commun 263: 681-684, 1999.
31. Moens AL, Kass DA. Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol 26: 2439-2444, 2006.
32. Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery compliance in postmenopausal women. Hypertension 45: 1107-1112, 2005.
33. Moreau KL, Meditz A, Deane KD, Kohrt WM. Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogendeficient postmenopausal women. Am J Physiol Heart Circ Physiol 302: H1211-H1218, 2012.
34. Munzel T, Daiber A, Ullrich V, Mulsch A. Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. Arterioscler Thromb Vasc Biol 25: 1551-1557, 2005.
35. Pierce GL. Oral BH4: A novel remedy for age-related skin microvascular impairment during heat stress or fool's elixir? J Appl Physiol; doi:10.1152/japplphysiol.00785.2013.
36. Pierce GL, Jablonski KL, Walker AE, Seibert SM, DeVan AE, Black SM, Sharma S, Seals DR. Tetrahydrobiopterin supplementation enhances carotid artery compliance in healthy older men: a pilot study. Am J Hypertens 25: 1050-1054, 2012.
37. Porkert M, Sher S, Reddy U, Cheema F, Niessner C, Kolm P, Jones DP, Hooper C, Taylor WR, Harrison D, Quyyumi AA. Tetrahydrobiopterin: a novel antihypertensive therapy. J Hum Hypertens 22: 401-407, 2008.
38. Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 95: 939-950, 1998.
39. Roddie IC, Shepherd JT, Whelan RF. The contribution of constrictor and dilator nerves to the skin vasodilatation during body heating. J Physiol 136: 489-497, 1957.
40. Sanford M, Keating GM. Sapropterin: a review of its use in the treatment of primary hyperphenylalaninaemia. Drugs 69: 461-476, 2009.
41. 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 85: 830-834, 1998.
42. Stanhewicz AE, Bruning RS, Smith CJ, Kenney WL, Holowatz LA. Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin. J Appl Physiol 112: 791-797, 2012.
43. Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BS, Karoui H, Tordo P, Pritchard KA Jr. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95: 9220-9225, 1998.
44. Whitney RJ. The measurement of changes in human limb-volume by means of a mercury-inrubber strain gauge. J Physiol 109: Proc, 5, 1949.
45. Wong BJ, Wilkins BW, Minson CT. H1 but not H2 histamine receptor activation contributes to the rise in skin blood flow during whole body heating in humans. J Physiol 560: 941-948, 2004.