Jornal Vascular Brasileiro
https://www.jvascbras.org/article/doi/10.1590/S1677-54492010000200007
Jornal Vascular Brasileiro
Review Article

Exercício físico, receptores β-adrenérgicos e resposta vascular

Physical exercise, β-adrenergic receptors, and vascular response

Alexandre Sérgio Silva; Angelina Zanesco

http://dx.doi.org/10.1590/S1677-54492010000200007 J Vasc Bras, vol.9, n2, p.47-56, 2010
PDF Português
PDF English
SciELO
Downloads: 1
Views: 859

Resumo

O exercício aeróbio promove efeitos benéficos na prevenção e tratamento de doenças como hipertensão arterial, aterosclerose, insuficiência venosa e doença arterial periférica. Os receptores β-adrenérgicos estão presentes em várias células. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardíaco e relaxamento vascular. Embora os efeitos do exercício tenham sido investigados em receptores cardíacos, estudos focados nos vasos são escassos e controversos. Esta revisão abordará os efeitos do exercício físico sobre os receptores β-adrenérgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. Em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercício físico sobre a resposta relaxante. Assim, os efeitos do exercício na sensibilidade β-adrenérgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular é um campo aberto para a descoberta de novos compostos e avanços na prática clínica.

Palavras-chave

Receptores β-adrenérgicos, pressão arterial, músculo liso vascular, exercício físico

Abstract

Aerobic exercise promotes beneficial effects on the prevention and treatment of diseases such as arterial hypertension, atherosclerosis, venous insufficiency, and peripheral arterial disease. β-adrenergic receptors are present in a variety of cells. In the cardiovascular system, β-adrenergic receptors promote positive inotropic and chronotropic response and vasorelaxation. Although the effect of exercise training has been largely studied in the cardiac tissue, studies focused on the vascular tissue are rare and controversial. This review examines the data from studies using animal and human models to determine the effect of physical exercise on the relaxing response mediated by β-adrenergic receptors as well as the cellular mechanisms involved in this response. Studies have shown reduction, increase, or no effect of physical exercise on the relaxing response mediated by β-adrenergic receptors. Thus, the effects of exercise on the vascular β-adrenergic sensitivity should be more deeply investigated. Furthermore, the physiopathology of the vascular system is an open field for the discovery of new compounds and advances in the clinical practice.

Keywords

β-adrenergic receptors, blood pressure, vascular smooth muscle, physical exercise

References

Schramm JMA, Oliveira AF, Leite IC. Transição epidemiológica e o estudo de carga de doença no Brasil. Cienc Saude Coletiva. 2004;9:897-908.

Schainfeld RM. Management of peripheral arterial disease and intermittent claudication. J Am Board Fam Pract. 2001;14:443-50.

Makdisse M, Pereira Ada C, Brasil Dde P. Prevalence and risk factors associated with peripheral arterial disease in the Hearts of Brazil Project. Arq Bras Cardiol. 2008;91:370-82.

Chakravarthy MV, Joyner MJ, Booth FW. An obligation for primary care physicians to prescribe physical activity to sedentary patients to reduce the risk of chronic health conditions. Mayo Clin Proc. 2002;77:165-73.

Zanesco A, Antunes E. Effects of exercise training on the cardiovascular system: pharmacological approaches. Pharmacol Ther. 2007;114:307-17.

Zago AS, Zanesco A. Nitric oxide: cardiovascular disease and physical exercise. Arq Bras Cardiol. 2006;81:264-70.

Milani RV, Lavie CJ. The role of exercise training in peripheral arterial disease. Vasc Med. 2007;12:351-8.

da Cunha-Filho IT, Pereira DA, de Carvalho AM, Campedeli L, Soares M, de Sousa Freitas J. The reliability of walking tests in people with claudication. Am J Phys Med Rehabil. 2007;86:574-82.

Yoshida RA, Matida CK, Sorbreira ML. Comparative study of evolution and survival of patients with intermittent claudication, with or without limitation for exercises, followed in a specific outpatient setting. J Vasc Bras. 2008;7:112-22.

Dawson DL. Comparative effects of cilostazol and other therapies for intermittent claudication. Am J Cardiol. 2001;87:19D-27D.

Klonizakis M, Tew G, Michaels J, Saxton J. Impaired microvascular endothelial function is restored by acute lower-limb exercise in post-surgical varicose vein patients. Microvasc Res. 2009;77:158-62.

Krieger EM, Brum PC, Negrao CE. State-of-the-Art lecture: influence of exercise training on neurogenic control of blood pressure in spontaneously hypertensive rats. Hypertension. 1999;34:720-3.

Hiatt WR, Regensteiner JG, Wolfel EE, Carry MR, Brass EP. Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease. J Appl Physiol. 1996;81:780-8.

Dessy C, Moniotte S, Ghisdal P, Havaux X, Noirhomme P, Balligand JL. Endothelial beta3-adrenoceptors mediate vasorelaxation of human coronary microarteries through nitric oxide and endothelium-dependent hyperpolarization. Circulation. 2004;110:948-54.

Webb RC. Smooth muscle contraction and relaxation. Adv Physiol Educ. 2003;27(1-4):201-6.

Zanesco A, Antunes E. Células endoteliais. Células. 2005:184-91.

Edwards DH, Li Y, Griffith TM. Hydrogen peroxide potentiates the EDHF phenomenon by promoting endothelial Ca2+ mobilization. Arterioscler Thromb Vasc Biol. 2008;28:1774-81.

Wagner CA. Hydrogen sulfide: a new gaseous signal molecule and blood pressure regulator. J Nephrol. 2009;22:173-6.

Langer SZ. Presynaptic regulation of catecholamine release. Biochem Pharmacol. 1974;23:1793-800.

Starke K. Alpha-adrenoceptor subclassification. Rev Physiol Biochem Pharmacol. 1981;88:199-236.

Ford AP, Williams TJ, Blue DR, Clarke DE. Alpha 1-adrenoceptor classification: sharpening Occam's razor. Trends Pharmacol Sci. 1994;15:167-70.

De Galan BE, De Mol P, Wennekes L, Schouwenberg BJ, Smits P. Preserved sensitivity to beta2-adrenergic receptor agonists in patients with type 1 diabetes mellitus and hypoglycemia unawareness. J Clin Endocrinol Metab. 2006;91:2878-81.

Palmer JP, Halter J, Werner PL. Differential effect of isoproterenol on acute glucagon and insulin release in man. Metabolism. 1979;28:237-40.

Nonogaki K. New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia. 2000;43:533-49.

Mauriege P, Imbeault P, Langin D. Regional and gender variations in adipose tissue lipolysis in response to weight loss. J Lipid Res. 1999;40:1559-71.

Lands AM, Luduena FP, Buzzo HJ. Differentiation of receptors responsive to isoproterenol. Life Sci. 1967;6:2241-9.

Emorine LJ, Marullo S, Briend-Sutren MM. Molecular characterization of the human beta 3-adrenergic receptor. Science. 1989;245:1118-21.

Cohen ML, Bloomquist W, Kriauciunas A, Shuker A, Calligaro D. Aryl propanolamines: comparison of activity at human beta3 receptors, rat beta3 receptors and rat atrial receptors mediating tachycardia. Br J Pharmacol. 1999;126:1018-24.

Roberts SJ, Russell FD, Molenaar P, Summers RJ. Characterization and localization of atypical beta-adrenoceptors in rat ileum. Br J Pharmacol. 1995;116:2549-56.

Molenaar P, Roberts SJ, Kim YS, Pak HS, Sainz RD, Summers RJ. Localization and characterization of two propranolol resistant (-) [125I]cyanopindolol binding sites in rat skeletal muscle. Eur J Pharmacol. 1991;209:257-62.

Sarsero D, Molenaar P, Kaumann AJ, Freestone NS. Putative beta 4-adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (-)-[3H]-CGP 12177 binding. Br J Pharmacol. 1999;128:1445-60.

Roberts SJ, Molenaar P, Summers RJ. Characterization of propranolol-resistant (-)-[125I]-cyanopindolol binding sites in rat soleus muscle. Br J Pharmacol. 1993;109:344-52.

Kaumann AJ, Molenaar P. Modulation of human cardiac function through 4 beta-adrenoceptor populations. Naunyn Schmiedebergs Arch Pharmacol. 1997;355:667-81.

Granneman JG. The putative beta4-adrenergic receptor is a novel state of the beta1-adrenergic receptor. Am J Physiol Endocrinol Metab. 2001;280:E199-202.

Konkar AA, Zhai Y, Granneman JG. beta1-adrenergic receptors mediate beta3-adrenergic-independent effects of CGP 12177 in brown adipose tissue. Mol Pharmacol. 2000;57:252-8.

Lewis CJ, Gong H, Brown MJ, Harding SE. Overexpression of beta 1-adrenoceptors in adult rat ventricular myocytes enhances CGP 12177A cardiostimulation: implications for 'putative' beta 4-adrenoceptor pharmacology. Br J Pharmacol. 2004;141:813-24.

Baker JG. Evidence for a secondary state of the human beta3-adrenoceptor. Mol Pharmacol. 2005;68:1645-55.

Jost P, Fasshauer M, Kahn CR. Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes. Am J Physiol Endocrinol Metab. 2002;283:E146-53.

Bowyer L, Brown MA, Jones M. Vascular reactivity in men and women of reproductive age. Am J Obstet Gynecol. 2001;185:88-96.

Kneale BJ, Chowienczyk PJ, Brett SE, Coltart DJ, Ritter JM. Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature. J Am Coll Cardiol. 2000;36:1233-8.

Guimaraes S, Moura D. Vascular adrenoceptors: an update. Pharmacol Rev. 2001;53:319-56.

O'Donnell SR, Wanstall JC. Responses to the beta 2-selective agonist procaterol of vascular and atrial preparations with different functional beta-adrenoceptor populations. Br J Pharmacol. 1985;84:227-35.

Stein CM, Deegan R, Wood AJ. Lack of correlation between arterial and venous beta-adrenergic receptor sensitivity. Hypertension. 1997;29:1273-7.

Yamazaki Y, Takeda H, Akahane M, Igawa Y, Nishizawa O, Ajisawa Y. Species differences in the distribution of beta-adrenoceptor subtypes in bladder smooth muscle. Br J Pharmacol. 1998;124:593-9.

Goldie RG, Papadimitriou JM, Paterson JW, Rigby PJ, Spina D. Autoradiographic localization of beta-adrenoceptors in pig lung using [125I]-iodocyanopindolol. Br J Pharmacol. 1986;88:621-8.

Pourageaud F, Leblais V, Bellance N, Marthan R, Muller B. Role of beta2-adrenoceptors (beta-AR), but not beta1-, beta3-AR and endothelial nitric oxide, in beta-AR-mediated relaxation of rat intrapulmonary artery. Naunyn Schmiedebergs Arch Pharmacol. 2005;372:14-23.

Chiba S, Tsukada M. Vascular responses to beta-adrenoceptor subtype-selective agonists with and without endothelium in rat common carotid arteries. J Auton Pharmacol. 2001;21:7-13.

Briones AM, Daly CJ, Jimenez-Altayo F, Martinez-Revelles S, Gonzalez JM, McGrath JC. Direct demonstration of beta1- and evidence against beta2- and beta3-adrenoceptors, in smooth muscle cells of rat small mesenteric arteries. Br J Pharmacol. 2005;146:679-91.

Chruscinski A, Brede ME, Meinel L, Lohse MJ, Kobilka BK, Hein L. Differential distribution of beta-adrenergic receptor subtypes in blood vessels of knockout mice lacking beta(1)- or beta(2)-adrenergic receptors. Mol Pharmacol. 2001;60:955-62.

Dessy C, Saliez J, Ghisdal P. Endothelial beta3-adrenoreceptors mediate nitric oxide-dependent vasorelaxation of coronary microvessels in response to the third-generation beta-blocker nebivolol. Circulation. 2005;112:1198-205.

Matsushita M, Tanaka Y, Koike K. Studies on the mechanisms underlying beta-adrenoceptor-mediated relaxation of rat abdominal aorta. J Smooth Muscle Res. 2006;42:217-25.

Tagaya E, Tamaoki J, Takemura H, Isono K, Nagai A. Relaxation of canine pulmonary arteries caused by stimulation of atypical beta-adrenergic receptors. Nihon Kokyuki Gakkai Zasshi. 1998;36:433-7.

Tagaya E, Tamaoki J, Takemura H, Isono K, Nagai A. Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cyclic adenosine monophosphate-dependent pathway. Lung. 1999;177:321-32.

Tamaoki J, Tagaya E, Isono K, Nagai A. Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cAMP-dependent pathway. Biochem Biophys Res Commun. 1998;248:722-7.

Brawley L, Shaw AM, MacDonald A. Beta 1-, beta 2- and atypical beta-adrenoceptor-mediated relaxation in rat isolated aorta. Br J Pharmacol. 2000;129:637-44.

Brawley L, Shaw AM, MacDonald A. Role of endothelium/nitric oxide in atypical beta-adrenoceptor-mediated relaxation in rat isolated aorta. Eur J Pharmacol. 2000;398:285-96.

Shafiei M, Mahmoudian M. Atypical beta-adrenoceptors of rat thoracic aorta. Gen Pharmacol. 1999;32:557-62.

Brahmadevara N, Shaw AM, MacDonald A. Evidence against beta 3-adrenoceptors or low affinity state of beta 1-adrenoceptors mediating relaxation in rat isolated aorta. Br J Pharmacol. 2003;138:99-106.

Brahmadevara N, Shaw AM, MacDonald A. ALpha1-adrenoceptor antagonist properties of CGP 12177A and other beta-adrenoceptor ligands: evidence against beta(3)- or atypical beta-adrenoceptors in rat aorta. Br J Pharmacol. 2004;142:781-7.

Kozlowska H, Szymska U, Schlicker E, Malinowska B. Atypical beta-adrenoceptors, different from beta 3-adrenoceptors and probably from the low-affinity state of beta 1-adrenoceptors, relax the rat isolated mesenteric artery. Br J Pharmacol. 2003;140:3-12.

Xu B, Huang Y. Different mechanisms mediate beta adrenoceptor stimulated vasorelaxation of coronary and femoral arteries. Acta Pharmacol Sin. 2000;21:309-12.

Xu B, Li J, Gao L, Ferro A. Nitric oxide-dependent vasodilatation of rabbit femoral artery by beta(2)-adrenergic stimulation or cyclic AMP elevation in vivo. Br J Pharmacol. 2000;129:969-74.

Phillips JK, Hickey H, Hill CE. Heterogeneity in mechanisms underlying vasodilatory responses in small arteries of the rat hepatic mesentery. Auton Neurosci. 2000;83:159-70.

Queen LR, Ferro A. Beta-adrenergic receptors and nitric oxide generation in the cardiovascular system. Cell Mol Life Sci. 2006;63:1070-83.

Raymond JR, Hnatowich M, Lefkowitz RJ, Caron MG. Adrenergic receptors: Models for regulation of signal transduction processes. Hypertension. 1990;15:119-31.

Birnbaumer L. Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits. Cell. 1992;71:1069-72.

Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980;284:17-22.

Song Y, Simard JM. beta-Adrenoceptor stimulation activates large-conductance Ca2+-activated K+ channels in smooth muscle cells from basilar artery of guinea pig. Pflugers Arch. 1995;430:984-93.

Akimoto Y, Horinouchi T, Shibano M, Matsushita M, Yamashita Y, Okamoto T. Nitric oxide (NO) primarily accounts for endothelium-dependent component of beta-adrenoceptor-activated smooth muscle relaxation of mouse aorta in response to isoprenaline. J Smooth Muscle Res. 2002;38:87-99.

Tang ZL, Wu WJ, Xiong XM. Influence of endothelium on responses of isolated dog coronary artery to beta-adrenoceptor agonists. Zhongguo Yao Li Xue Bao. 1995;16:357-60.

Marsen TA, Egink G, Suckau G, Baldamus CA. Tyrosine-kinase-dependent regulation of the nitric oxide synthase gene by endothelin-1 in human endothelial cells. Pflugers Arch. 1999;438:538-44.

Schmitt JM, Stork PJ. beta 2-adrenergic receptor activates extracellular signal-regulated kinases (ERKs) via the small G protein rap1 and the serine/threonine kinase B-Raf. J Biol Chem. 2000;275:25342-50.

Isenovic E, Walsh MF, Muniyappa R, Bard M, Diglio CA, Sowers JR. Phosphatidylinositol 3-kinase may mediate isoproterenol-induced vascular relaxation in part through nitric oxide production. Metabolism. 2002;51:380-6.

Murad F, Forstermann U, Nakane M. The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication. Adv Second Messenger Phosphoprotein Res. 1993;28:101-9.

Omori K, Kotera J. Overview of PDEs and their regulation. Circ Res. 2007;100:309-27.

Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov. 2006;5:755-68.

Woodman CR, Thompson MA, Turk JR, Laughlin MH. Endurance exercise training improves endothelium-dependent relaxation in brachial arteries from hypercholesterolemic male pigs. J Appl Physiol. 2005;99:1412-21.

Woodman CR, Turk JR, Rush JW, Laughlin MH. Exercise attenuates the effects of hypercholesterolemia on endothelium-dependent relaxation in coronary arteries from adult female pigs. J Appl Physiol. 2004;96:1105-13.

Higashi Y, Yoshizumi M. Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther. 2004;102:87-96.

Parker JL, Mattox ML, Laughlin MH. Contractile responsiveness of coronary arteries from exercise-trained rats. J Appl Physiol. 1997;83:434-43.

McAllister RM, Kimani JK, Webster JL, Parker JL, Laughlin MH. Effects of exercise training on responses of peripheral and visceral arteries in swine. J Appl Physiol. 1996;80:216-25.

Graham DA, Rush JW. Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats. J Appl Physiol. 2004;96:2088-96.

Johnson LR, Rush JW, Turk JR, Price EM, Laughlin MH. Short-term exercise training increases ACh-induced relaxation and eNOS protein in porcine pulmonary arteries. J Appl Physiol. 2001;90:1102-10.

De Moraes R, Gioseffi G, Nobrega AC, Tibirica E. Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits. J Appl Physiol. 2004;97:683-8.

Kang KB, Rajanayagam MA, van der Zypp A, Majewski H. A role for cyclooxygenase in aging-related changes of beta-adrenoceptor-mediated relaxation in rat aortas. Naunyn Schmiedebergs Arch Pharmacol. 2007;375:273-81.

van der Zypp A, Kang KB, Majewski H. Age-related involvement of the endothelium in beta-adrenoceptor-mediated relaxation of rat aorta. Eur J Pharmacol. 2000;397:129-38.

Arribas SM, Vila E, McGrath JC. Impairment of vasodilator function in basilar arteries from aged rats. Stroke. 1997;28:1812-20.

Gaballa MA, Eckhart AD, Koch WJ, Goldman S. Vascular beta-adrenergic receptor adenylyl cyclase system in maturation and aging. J Mol Cell Cardiol. 2000;32:1745-55.

Gaballa MA, Eckhart A, Koch WJ, Goldman S. Vascular beta-adrenergic receptor system is dysfunctional after myocardial infarction. Am J Physiol Heart Circ Physiol. 2001;280:H1129-35.

Blankesteijn WM, Raat NJ, Willems PH, Thien T. beta-Adrenergic relaxation in mesenteric resistance arteries of spontaneously hypertensive and Wistar-Kyoto rats: the role of precontraction and intracellular Ca2+. J Cardiovasc Pharmacol. 1996;27:27-32.

Lu Z, Qu P, Xu K, Han C. beta-Adrenoceptors in endothelium of rabbit coronary artery and alteration in atherosclerosis. Biol Signals. 1995;4(3):150-9.

Mallem Y, Holopherne D, Reculeau O, Le Coz O, Desfontis JC, Gogny M. Beta-adrenoceptor-mediated vascular relaxation in spontaneously hypertensive rats. Auton Neurosci. 2005;118:61-7.

Werstiuk ES, Lee RM. Vascular beta-adrenoceptor function in hypertension and in ageing. Can J Physiol Pharmacol. 2000;78:433-52.

Harri MN. Physical training under the influence of beta-blockade in rats: II. Effects on vascular reactivity. Eur J Appl Physiol Occup Physiol. 1979;42:151-7.

DiCarlo SE, Blair RW, Bishop VS, Stone HL. Role of beta 2-adrenergic receptors on coronary resistance during exercise. J Appl Physiol. 1988;64:2287-93.

Traverse JH, Altman JD, Kinn J, Duncker DJ, Bache RJ. Effect of beta-adrenergic receptor blockade on blood flow to collateral-dependent myocardium during exercise. Circulation. 1995;91:1560-7.

Leosco D, Iaccarino G, Cipolletta E, De Santis D, Pisani E, Trimarco V. Exercise restores beta-adrenergic vasorelaxation in aged rat carotid arteries. Am J Physiol Heart Circ Physiol. 2003;285:H369-74.

Donato AJ, Lesniewski LA, Delp MD. Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles. J Physiol. 2007;579:115-25.

Drieu la Rochelle C, Berdeaux A, Richard V, Giudicelli JF. Coronary effects of a combined beta adrenoceptor blocking and calcium antagonist therapy in running dogs. J Cardiovasc Pharmacol. 1991;18:904-10.

Sociedade Brasileira de Angiologia e Cirurgia Vascular (SBACV)"> Sociedade Brasileira de Angiologia e Cirurgia Vascular (SBACV)">
5dded7940e882571627279a4 jvb Articles
1677-7301 (Electronic)
J Vasc Bras ©2024 All rights reserved.

J Vasc Bras

Share this page
Page Sections