(Circulation. 1997;95:2293-2297.)
© 1997 American Heart Association, Inc.
Articles |
Effects of Inhibition of the L-Arginine/Nitric Oxide Pathway on Vasodilation Caused by ß-Adrenergic Agonists in Human Forearm
From the Department of Clinical Pharmacology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, UK.
Correspondence to Dr M. Dawes, Department of Clinical Pharmacology, St Thomas' Hospital, Lambeth Palace Rd, London, SE1 7EH UK. E-mail j.ritter{at}umds.ac.uk
Background We examined whether vasodilator responses to ß-agonists in human forearm vasculature are mediated in part through the nitric oxide pathway.
Methods and Results We measured forearm blood flow responses to brachial artery infusions of ß-adrenergic agonists in healthy men. Salbutamol was more than 100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5 nmol·min-1) did not cause tachyphylaxis to an identical repeated infusion after a 24-minute recovery period. Vasodilators were infused with this sequence during coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 µmol·min-1), an inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol·min-1) by 59±7% (n=5) and inhibited those to salbutamol (0.3 to 3.5 nmol·min-1) by 52±6% (n=8). L-NMMA had no significant effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol·min-1, n=8), verapamil (20 to 80 nmol·min-1, n=8), or prostacyclin (0.08 to 0.24 nmol·min-1, n=8).
Conclusions These results suggest that ß-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through ß2-adrenergic receptors and are dependent on nitric oxide synthesis.
Key Words: blood flow • endothelium-derived factors • receptors, adrenergic, beta • vasodilation
This article has been cited by other articles:
 |
|
 |
|
  E. S. Mendes, G. Horvath, P. Rebolledo, M. E. Monzon, S. M. Casalino-Matsuda, and A. Wanner Effect of an inhaled glucocorticoid on endothelial function in healthy smokers J Appl Physiol, July 1, 2008; 105(1): 54 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L Browne, D. R Meeking, S. Allard, L. J Munday, K. M Shaw, and M. H Cummings Vasodilator prostanoids compensate for attenuated nitric oxide mediated vasodilation in type 1 diabetes The British Journal of Diabetes & Vascular Disease, November 1, 2007; 7(6): 288 - 294. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Moradkhan, P. McQuillan, C. Hogeman, A. Leuenberger, L. Linton-Frazier, and U. A. Leuenberger Metabolic forearm vasodilation is enhanced following Bier block with phentolamine Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2289 - H2295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Pellinger and J. R. Halliwill Effect of propranolol on sympathetically mediated leg vasoconstriction in humans J. Physiol., September 1, 2007; 583(2): 797 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhang, C. M. Hayden, S-K. Khoo, P. Candelaria, I. A. Laing, S. Turner, P. Franklin, S. Stick, L. Landau, J. Goldblatt, et al. {beta}2-Adrenoceptor polymorphisms and asthma phenotypes: interactions with passive smoking Eur. Respir. J., July 1, 2007; 30(1): 48 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Mendes, M. A. Campos, and A. Wanner Airway Blood Flow Reactivity in Healthy Smokers and in Ex-Smokers With or Without COPD. Chest, April 1, 2006; 129(4): 893 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Swampillai, S. Doshi, A. G Fraser, J. Goodfellow, and C. J. Jones Review: Clinical assessment of endothelial function -- an update The British Journal of Diabetes & Vascular Disease, March 1, 2005; 5(2): 72 - 76. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Dwivedi, S. Saha, P.J. Chowienczyk, and J.M. Ritter Block of Inward Rectifying K+ Channels (KIR) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): e7 - e9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. McEniery, M. Schmitt, A. Qasem, D. J. Webb, A. P. Avolio, I. B. Wilkinson, and J. R. Cockcroft Nebivolol Increases Arterial Distensibility In Vivo Hypertension, September 1, 2004; 44(3): 305 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tawakol, T. Omland, and M. A. Creager Direct effect of ethanol on human vascular function Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2468 - H2473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Kahn, A. Sherwood, J. W. Hughes, J. A. Blumenthal, E. C. Suarez, and A. L. Hinderliter HOSTILITY, CORONARY RISK, AND {alpha}-ADRENERGIC TO {beta}-ADRENERGIC RECEPTOR DENSITY RATIO * Response Psychosom Med, March 1, 2004; 66(2): 289 - 290. [Full Text]
|
|
|
|
 |
|
 D. Striimper, M. Durieux, and P. Roekaerts Endothelial and Microvascular Function Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 225 - 238. [Abstract] [PDF]
|
|
|
|
|
|
J. A. S. Barreto-Filho, F. M. Consolim-Colombo, G. M. Guerra-Riccio, R. D. Santos, A. P. Chacra, H. F. Lopes, S. H. Teixeira, T. Martinez, J. E. Krieger, and E. M. Krieger Hypercholesterolemia Blunts Forearm Vasorelaxation and Enhances the Pressor Response During Acute Systemic Hypoxia Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1660 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W Koch, U. A Leuenberger, and D. N Proctor Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation J. Physiol., August 15, 2003; 551(1): 337 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Leosco, G. Iaccarino, E. Cipolletta, D. De Santis, E. Pisani, V. Trimarco, N. Ferrara, P. Abete, D. Sorriento, F. Rengo, et al. Exercise restores {beta}-adrenergic vasorelaxation in aged rat carotid arteries Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H369 - H374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. D Garovic, M. J Joyner, N. M Dietz, E. Boerwinkle, and S. T Turner {beta}2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans J. Physiol., January 15, 2003; 546(2): 583 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schalcher, K. Schad, H. P. Brunner-La Rocca, R. Schindler, E. Oechslin, C. Scharf, G. Suetsch, O. Bertel, and W. Kiowski Interaction of Sildenafil With cAMP-Mediated Vasodilation In Vivo Hypertension, November 1, 2002; 40(5): 763 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Hayward, M. Kraidly, C. M. Webb, and P. Collins Assessment of endothelial function using peripheral waveform analysis: A clinical application J. Am. Coll. Cardiol., August 7, 2002; 40(3): 521 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Iaccarino, E. Cipolletta, A. Fiorillo, M. Annecchiarico, M. Ciccarelli, V. Cimini, W. J. Koch, and B. Trimarco {beta}2-Adrenergic Receptor Gene Delivery to the Endothelium Corrects Impaired Adrenergic Vasorelaxation in Hypertension Circulation, July 16, 2002; 106(3): 349 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A DeSouza, C. M Clevenger, J. J Greiner, D. T Smith, G. L Hoetzer, L. F Shapiro, and B. L Stauffer Evidence for agonist-specific endothelial vasodilator dysfunction with ageing in healthy humans J. Physiol., July 1, 2002; 542(1): 255 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. B. Wilkinson, I. R. Hall, H. MacCallum, I. S. Mackenzie, C. M. McEniery, B. J. van der Arend, Y.-E. Shu, L. S. MacKay, D. J. Webb, and J. R. Cockcroft Pulse-Wave Analysis: Clinical Evaluation of a Noninvasive, Widely Applicable Method for Assessing Endothelial Function Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J Weisbrod, C. T Minson, M. J Joyner, and J. R Halliwill Effects of regional phentolamine on hypoxic vasodilatation in healthy humans J. Physiol., December 1, 2001; 537(2): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chruscinski, M. E. Brede, L. Meinel, M. J. Lohse, B. K. Kobilka, and L. Hein Differential Distribution of beta -Adrenergic Receptor Subtypes in Blood Vessels of Knockout Mice Lacking beta 1- or beta 2-Adrenergic Receptors Mol. Pharmacol., November 1, 2001; 60(5): 955 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guimaraes and D. Moura Vascular Adrenoceptors: An Update Pharmacol. Rev., June 1, 2001; 53(2): 319 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Torp, M. E. Tschakovsky, J. R. Halliwill, C. T. Minson, and M. J. Joyner {beta}-Receptor agonist activity of phenylephrine in the human forearm J Appl Physiol, May 1, 2001; 90(5): 1855 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Lamping Interactions Between NO and cAMP in the Regulation of Vascular Tone Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 729 - 730. [Full Text] [PDF]
|
|
|
|
|
|
A. Rozanski, E. Qureshi, M. Bauman, G. Reed, G. Pillar, and G. A. Diamond Peripheral Arterial Responses to Treadmill Exercise Among Healthy Subjects and Atherosclerotic Patients Circulation, April 24, 2001; 103(16): 2084 - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Gaballa, A. Eckhart, W. J. Koch, and S. Goldman Vascular {beta}-adrenergic receptor system is dysfunctional after myocardial infarction Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1129 - H1135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Walker, T. S. Dean, T. A. B. Sanders, G. Jackson, J. M. Ritter, and P. J. Chowienczyk The Phytoestrogen Genistein Produces Acute Nitric Oxide-Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17{beta}-Estradiol Circulation, January 16, 2001; 103(2): 258 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Kneale, P. J. Chowienczyk, S. E. Brett, D. J. Coltart, and J. M. Ritter Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1233 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. GROTE, H. KRAICZI, and J. HEDNER Reduced alpha - and beta 2-Adrenergic Vascular Response in Patients with Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1480 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Cockcroft, A. G. Gazis, D. J. Cross, A. Wheatley, J. Dewar, I. P. Hall, and J. P. Noon {beta}2-Adrenoceptor Polymorphism Determines Vascular Reactivity in Humans Hypertension, September 1, 2000; 36(3): 371 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fichtlscherer, G. Rosenberger, D. H. Walter, S. Breuer, S. Dimmeler, and A. M. Zeiher Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease Circulation, August 29, 2000; 102(9): 1000 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. W. Broeders, P. A. Doevendans, B. C. A. M. Bekkers, R. Bronsaer, E. van Gorsel, J. W. M. Heemskerk, M. G. A. o. Egbrink, E. van Breda, R. S. Reneman, and R. van der Zee Nebivolol: A Third-Generation {beta}-Blocker That Augments Vascular Nitric Oxide Release : Endothelial {beta}2-Adrenergic Receptor-Mediated Nitric Oxide Production Circulation, August 8, 2000; 102(6): 677 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S Reed, M. E Tschakovsky, C. T Minson, J. R Halliwill, K. D Torp, L. A Nauss, and M. J Joyner Skeletal muscle vasodilatation during sympathoexcitation is not neurally mediated in humans J. Physiol., May 15, 2000; 525(1): 253 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Chowienczyk, R. P. Kelly, H. MacCallum, S. C. Millasseau, T. L. G. Andersson, R. G. Gosling, J. M. Ritter, and E. E. Anggard Photoplethysmographic assessment of pulse wave reflection: Blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2007 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuda, T. Toriumi, H. Xu, H. Kinoshita, H. Nishimaki, S. Kokubun, N. Fujiwara, H. Fujihara, and K. Shimoji Enhanced beta -receptor-mediated vasorelaxation in hypoxic porcine coronary artery Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1447 - H1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sherwood, K. Johnson, J. A. Blumenthal, and A. L. Hinderliter Endothelial Function and Hemodynamic Responses During Mental Stress Psychosom Med, May 1, 1999; 61(3): 365 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, and J. A. Panza Attenuation of Cyclic Nucleotide–Mediated Smooth Muscle Relaxation in Blacks as a Cause of Racial Differences in Vasodilator Function Circulation, January 12, 1999; 99(1): 90 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, C. M. Kilcoyne, R. O. Cannon III, and J. A. Panza Impairment of the nitric oxide-mediated vasodilator response to mental stress in hypertensive but not in hypercholesterolemic patients J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1207 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Stein, N. Brown, D. E. Vaughan, C. C. Lang, and A. J. J. Wood Regulation of local tissue-type plasminogen activator release by endothelium-dependent and endothelium-independent agonists in human vasculature J. Am. Coll. Cardiol., July 1, 1998; 32(1): 117 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Laine, M. J. Knuuti, U. Ruotsalainen, T. Utriainen, V. Oikonen, M. Raitakari, M. Luotolahti, O. Kirvela, P. Vicini, C. Cobelli, et al. Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension Circulation, June 2, 1998; 97(21): 2146 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cardillo and J. A Panza Impaired endothelial regulation of vascular tone in patients with systemic arterial hypertension Vascular Medicine, May 1, 1998; 3(2): 138 - 144. [Abstract] [PDF]
|
|
|
|
|
|
C. Cardillo, C. M. Kilcoyne, A. A. Quyyumi, R. O. Cannon III, and J. A. Panza Selective Defect in Nitric Oxide Synthesis May Explain the Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension Circulation, March 10, 1998; 97(9): 851 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Eisenach, E. S. Clark, N. Charkoudian, F. A. Dinenno, J. L. D. Atkinson, R. D. Fealey, N. M. Dietz, and M. J. Joyner Effects of chronic sympathectomy on vascular function in the human forearm J Appl Physiol, May 1, 2002; 92(5): 2019 - 2025. [Abstract] [Full Text] [PDF]
|
|