title: Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle.
abstract: A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K⁺-mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K⁺-mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K⁺-mediated vasodilation, BaCl₂ and ouabain were infused intra-arterially to inhibit inwardly rectifying K⁺ channels and Na⁺-K⁺-ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred via NG-monomethyl-L-arginine (L-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. In protocol 1 (n = 8), BaCl₂ + ouabain reduced peak vasodilation (range: 30-45%, P < 0.05) and total postcontraction vasodilation (area under the curve, ~55-75% from control) at all intensities. Contrary to our hypothesis, L-NMMA + ketorolac had a further impact (peak: ~60% and area under the curve: ~80% from control). In protocol 2 (n = 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K⁺-mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.
authors: Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523, USA.
authors: Anne R
authors: AR
authors: Crecelius
authors: Brett S
authors: BS
authors: Kirby
authors: Gary J
authors: GJ
authors: Luckasen
authors: Dennis G
authors: DG
authors: Larson
authors: Frank A
authors: FA
authors: Dinenno
mesh_terms: D000328:Adult; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014664:Vasodilation
chemical_list: D016861:Cyclooxygenase Inhibitors; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011453:Prostaglandins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
keywords: exercise; hyperemia; potassium
references: J Physiol. 2007 Sep 15;583(Pt 3):861-74
references: 17495044
references: J Appl Physiol (1985). 2003 Jan;94(1):6-10
references: 12391132
references: Am J Physiol. 1994 Jul;267(1 Pt 2):H326-32
references: 8048598
references: Am J Physiol. 1978 Nov;235(5):H494-504
references: 727272
references: J Physiol. 1935 Nov 22;85(3):375-99
references: 16994720
references: Biophys J. 1980 Jun;30(3):473-88
references: 6266531
references: J Physiol. 2011 Jul 15;589(Pt 14):3671-83
references: 21624968
references: Nature. 1998 Nov 19;396(6708):269-72
references: 9834033
references: Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1633-41
references: 20817831
references: Acta Physiol Scand. 1989 Aug;136(4):551-9
references: 2782102
references: J Physiol. 2009 May 1;587(Pt 9):1989-2003
references: 19307300
references: J Physiol. 2003 Jun 15;549(Pt 3):985-94
references: 12730336
references: Circ Res. 1975 Sep;37(3):325-32
references: 1157221
references: Am J Physiol. 1979 Mar;236(3):H480-6
references: 426084
references: J Physiol. 2007 Feb 15;579(Pt 1):227-36
references: 17138603
references: J Physiol. 2004 Jun 15;557(Pt 3):1013-20
references: 15073277
references: Microcirculation. 2004 Apr-May;11(3):279-93
references: 15280082
references: Am J Physiol. 1967 Sep;213(3):683-9
references: 6036785
references: Acta Physiol Scand. 1971 Feb;81(2):157-63
references: 5552789
references: Am J Physiol. 1997 Jul;273(1 Pt 2):H156-63
references: 9249486
references: Am J Physiol. 1974 Sep;227(3):531-5
references: 4414768
references: Can J Physiol Pharmacol. 2004 Apr;82(4):282-7
references: 15181467
references: J Appl Physiol (1985). 2004 Feb;96(2):639-44
references: 14578368
references: Circ Res. 1978 Jan;42(1):35-42
references: 618600
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1302-10
references: 21784984
references: Acta Physiol (Oxf). 2012 May;205(1):103-12
references: 21981828
references: Circ Res. 1973 Sep;33(3):323-36
references: 4746721
references: J Appl Physiol (1985). 1996 Oct;81(4):1516-21
references: 8904562
references: J Physiol. 2008 Sep 1;586(17):4305-16
references: 18617568
references: J Physiol. 2011 Apr 15;589(Pt 8):1979-90
references: 21486803
references: Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H233-8
references: 10644603
references: J Physiol. 2007 Feb 15;579(Pt 1):175-86
references: 17138602
references: Hypertension. 2010 Dec;56(6):1102-8
references: 21041702
references: J Appl Physiol (1985). 1997 Dec;83(6):2037-42
references: 9390978
references: J Appl Physiol (1985). 1998 Nov;85(5):1649-54
references: 9804565
references: J Physiol. 2012 Nov 1;590(21):5349-59
references: 22777673
references: J Physiol. 2003 Nov 15;553(Pt 1):281-92
references: 12949223
references: J Physiol. 2006 Apr 15;572(Pt 2):561-7
references: 16497720
references: Am J Physiol. 1993 Oct;265(4 Pt 2):H1227-34
references: 8238409
references: J Physiol. 2007 Jun 1;581(Pt 2):841-52
references: 17363384
references: Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1963-70
references: 18310521
references: Acta Physiol (Oxf). 2013 May;208(1):74-87
references: 23297742
references: J Physiol. 2004 Jun 1;557(Pt 2):599-611
references: 15047770
references: Acta Physiol Scand. 1970 Sep;80(1):61-72
references: 5475332
references: Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H119-27
references: 16100250
references: Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):e7-9
references: 15591222
references: Hypertension. 2009 Jun;53(6):993-9
references: 19433775
references: Acta Physiol (Oxf). 2010 Aug;199(4):393-406
references: 20345408
references: J Physiol. 2010 Oct 15;588(Pt 20):4017-27
references: 20807789
references: Am J Physiol. 1987 Nov;253(5 Pt 2):H993-1004
references: 3318504
references: Microcirculation. 2005 Jan-Feb;12(1):113-27
references: 15804979
references: J Cardiovasc Pharmacol. 1992;19 Suppl 3:S6-10
references: 1376838
references: Exerc Sport Sci Rev. 2001 Oct;29(4):159-63
references: 11688788
references: J Appl Physiol (1985). 2004 Jul;97(1):393-403
references: 15220322
references: Exerc Sport Sci Rev. 2008 Jan;36(1):25-9
references: 18156950
references: J Appl Physiol (1985). 1998 Dec;85(6):2249-54
references: 9843549
references: J Appl Physiol. 1964 Jan;19:142-6
references: 14104271
references: J Physiol. 2007 Sep 15;583(Pt 3):855-60
references: 17640934
references: Am J Physiol. 1995 Apr;268(4 Pt 1):C799-822
references: 7733230
references: Am J Physiol. 1996 Oct;271(4 Pt 2):H1697-701
references: 8897965
references: J Physiol. 2007 Sep 15;583(Pt 3):825-33
references: 17615103
references: Med Sci Sports Exerc. 2003 Dec;35(12):2005-12
references: 14652495
references: Hypertension. 2009 Jun;53(6):973-8
references: 19414649
references: Circulation. 2002 Mar 19;105(11):1323-8
references: 11901043
references: Circ Res. 1974 Sep;35(3):384-90
references: 4417217
references: Circ Res. 1979 Jun;44(6):767-80
references: 428071
references: Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1319-28
references: 16617135
references: J Physiol. 2007 Jun 1;581(Pt 2):853-61
references: 17347273