title: Nitric oxide, but not vasodilating prostaglandins, contributes to the improvement of exercise hyperemia via ascorbic acid in healthy older adults.
abstract: Acute ascorbic acid (AA) administration increases muscle blood flow during dynamic exercise in older adults, and this is associated with improved endothelium-dependent vasodilation. We directly tested the hypothesis that increase in muscle blood flow during AA administration is mediated via endothelium-derived vasodilators nitric oxide (NO) and prostaglandins (PGs). In 14 healthy older adults (64 ± 3 yr), we measured forearm blood flow (FBF; Doppler ultrasound) during rhythmic handgrip exercise at 10% maximum voluntary contraction. After 5-min steady-state exercise with saline, AA was infused via brachial artery catheter for 10 min during continued exercise, and this increased FBF ∼25% from 132 ± 16 to 165 ± 20 ml/min (P < 0.05). AA was infused for the remainder of the study. Next, subjects performed a 15-min exercise bout in which AA + saline was infused for 5 min, followed by 5 min of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) and then 5 min of the cyclooxygenase inhibitor ketorolac (group 1). The order of inhibition was reversed in eight subjects (group 2). In group 1, independent NOS inhibition reduced steady-state FBF by ∼20% (P < 0.05), and subsequent PG inhibition had no impact on FBF (Δ 3 ± 5%). Similarly, in group 2, independent PG inhibition had little effect on FBF (Δ -4 ± 4%), whereas subsequent NO inhibition significantly decreased FBF by ∼20% (P < 0.05). In a subgroup of five subjects, we inhibited NO and PG synthesis before AA administration. In these subjects, there was a minimal nonsignificant improvement in FBF with AA infusion (Δ 7 ± 3%; P = nonsignificant vs. zero). Together, our data indicate that the increase in muscle blood flow during dynamic exercise with acute AA administration in older adults is mediated primarily via an increase in the bioavailability of NO derived from the NOS pathway.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado 80523-1582, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Crecelius
authors.forename: Brett S
authors.initials: BS
authors.lastname: Kirby
authors.forename: Wyatt F
authors.initials: WF
authors.lastname: Voyles
authors.forename: Frank A
authors.initials: FA
authors.lastname: Dinenno
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000975:Antioxidants; D011453:Prostaglandins; D009569:Nitric Oxide; D001205:Ascorbic Acid
references.citation: Ann N Y Acad Sci. 2004 Dec;1031:425-7
references.pmid: 15753187
references.citation: Circulation. 1996 Mar 15;93(6):1107-13
references.pmid: 8653830
references.citation: Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):697-705
references.pmid: 16424350
references.citation: Circ Res. 1998 Nov 2;83(9):916-22
references.pmid: 9797340
references.citation: Annu Rev Med. 1997;48:489-509
references.pmid: 9046979
references.citation: Hypertension. 1997 Mar;29(3):736-43
references.pmid: 9052889
references.citation: J Physiol. 2002 Sep 1;543(Pt 2):691-8
references.pmid: 12205200
references.citation: Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1963-70
references.pmid: 18310521
references.citation: Hypertension. 2009 Jun;53(6):993-9
references.pmid: 19433775
references.citation: Hypertension. 2001 Aug;38(2):274-9
references.pmid: 11509489
references.citation: J Physiol. 2005 Nov 1;568(Pt 3):1057-65
references.pmid: 16141271
references.citation: Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1023-31
references.pmid: 12738622
references.citation: J Biol Chem. 2001 Jan 5;276(1):40-7
references.pmid: 11022034
references.citation: J Physiol. 2009 May 1;587(Pt 9):1989-2003
references.pmid: 19307300
references.citation: Biochem Biophys Res Commun. 1975 Mar 17;63(2):463-8
references.pmid: 235924
references.citation: J Physiol. 2007 Feb 15;579(Pt 1):227-36
references.pmid: 17138603
references.citation: Exerc Sport Sci Rev. 1991;19:313-49
references.pmid: 1936089
references.citation: J Physiol. 1994 Oct 15;480 ( Pt 2):361-8
references.pmid: 7869251
references.citation: Microcirculation. 2006 Jun;13(4):315-27
references.pmid: 16611597
references.citation: J Physiol. 2004 Apr 1;556(Pt 1):315-24
references.pmid: 14754992
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R803-9
references.pmid: 16556903
references.citation: Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2576-84
references.pmid: 15271659
references.citation: Circulation. 2000 Jun 27;101(25):2896-901
references.pmid: 10869260
references.citation: J Appl Physiol (1985). 2003 Nov;95(5):1963-70
references.pmid: 12882993
references.citation: J Physiol. 2001 Feb 15;531(Pt 1):257-64
references.pmid: 11179408
references.citation: J Cardiovasc Pharmacol. 1996;27 Suppl 2:S9-12
references.pmid: 8723393
references.citation: J Physiol. 2003 Nov 15;553(Pt 1):281-92
references.pmid: 12949223
references.citation: J Physiol. 2004 Jun 1;557(Pt 2):599-611
references.pmid: 15047770
references.citation: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1870-5
references.pmid: 19767527
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12814-9
references.pmid: 11606734
references.citation: J Physiol. 2008 Feb 15;586(4):1161-8
references.pmid: 18063659
references.citation: Hypertension. 2009 Jun;53(6):973-8
references.pmid: 19414649
references.citation: Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1251-9
references.pmid: 12595287
references.citation: Lancet. 1989 Oct 28;2(8670):997-1000
references.pmid: 2572793
references.citation: Acta Physiol Scand. 1998 Mar;162(3):421-36
references.pmid: 9578388
references.citation: J Physiol. 2007 Jun 1;581(Pt 2):853-61
references.pmid: 17347273