Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals

Yrsa Bergmann Sverrisdóttir, Linda Marie Jansson, Ulrika Hägg, Li-Ming Gan, Yrsa Bergmann Sverrisdóttir, Linda Marie Jansson, Ulrika Hägg, Li-Ming Gan

Abstract

Background: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals.

Methods and results: In 10 healthy normotensive subjects (3 f/7 m), (age 37+/-11 yrs), (BMI 24+/-3 kg/m(2)) direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA) were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT) technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index), was within the normal range (1.9-3.3) and MSNA was as expected for age and gender (13-44 burst/minute). RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005). RH-PAT index and MSNA were reciprocally related to time (h/week) spent on physical activity (p = 0.005 and p = 0.006 respectively) and platelet concentration (PLT) (p = 0.02 and p = 0.004 respectively).

Conclusions: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular health.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Muscle sympathetic nerve activity (MSNA)…
Figure 1. Muscle sympathetic nerve activity (MSNA) expressed as burst frequency (bursts/minute) and reactive hyperemic index (%) in 10 healthy controls, r = −0.8, p = 0.005.
Figure 2. Physical activity expressed as hours…
Figure 2. Physical activity expressed as hours per week and a) muscle sympathetic nerve activity (MSNA) expressed as burst frequency (bursts/minute) and b) reactive hyperaemic index (%) in 10 healthy controls, (r = −0.79, p = 0.006 and r = 0.83, p = 0.004, respectively).

References

    1. Kaye DM, Lambert GW, Lefkovits J, Morris M, Jennings G, et al. Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. J Am Coll Cardiol. 1994;23:570–578.
    1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.
    1. Esler M, Kaye D. Sympathetic nervous system activation in essential hypertension, cardiac failure and psychosomatic heart disease. J Cardiovasc Pharmacol. 2000;35:S1–7.
    1. Sartori C, Lepori M, Scherrer U. Interaction between nitric oxide and the cholinergic and sympathetic nervous system in cardiovascular control in humans. Pharmacology & Therapeutics. 2005;106:209–220.
    1. Hijmering ML, Stroes ESG, Olijhoek J, Hutten BA, Blankestijn PJ, et al. Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. Journal of the American College of Cardiology. 2002;39:683–688.
    1. Forte P, Kneale BJ, Milne E, Chowienczyk PJ, Johnston A, et al. Evidence for a Difference in Nitric Oxide Biosynthesis Between Healthy Women and Men. Hypertension. 1998;32:730–734.
    1. Otto ME, Svatikova A, Barretto RBdM, Santos S, Hoffmann M, et al. Early Morning Attenuation of Endothelial Function in Healthy Humans. Circulation. 2004;109:2507–2510.
    1. Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic-Nerve Activity during Sleep in Normal Subjects. N Engl J Med. 1993;328:303–307.
    1. Hedblad B, Wikstrand J, Janzon L, Wedel H, Berglund G. Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness: Main Results From the {beta}-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). Circulation. 2001;103:1721–1726.
    1. Fagius J, Wallin BG. Long-term variability and reproducibility of resting human muscle nerve sympathetic activity at rest, as reassessed after a decade. Clin Auton Res. 1993;3:201–205.
    1. Franzoni F, Galetta F, Morizzo C, Lubrano V, Palombo C, et al. Effects of age and physical fitness on microcirculatory function. Clin Sci. 2004;106:329–335.
    1. Kubo SHSH. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation. 1991;84:1589–1596.
    1. Panza JA. Endothelial dysfunction in essential hypertension. Clin Cardiol. 1997;20:II-26–33.
    1. Boger RH. Nitric oxide and the mediation of the hemodynamic effects of growth hormone in humans. J Endocrinol Invest. 1999;22:75–81.
    1. Sverrisdottir YB, Elam M, Herlitz H, Bengtsson BA, Johannsson G. Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. J Clin Endocrinol Metab. 1998;83:1881–1885.
    1. Sverrisdottir YB, Johannsson G, Jungersten L, Wallin BG, Elam M. Is the somatotropic axis related to sympathetic nerve activity in healthy ageing men? J Hypertens. 2001;19:2019–2024.
    1. Sverrisdottir YB, Mogren T, Kataoka J, Janson P-O, Stener-Victorin E. Is Polycystic Ovary Syndrome Associated with High Sympathetic Nerve Activity and Size at Birth? Am J Physiol Endocrinol Metab. 2008:00725.02007.
    1. Fraga R, Franco FG, Roveda F, de Matos LN, Braga AM, et al. Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol. Eur J Heart Fail. 2007;9:630–636.
    1. Kingwell BABA. Nitric oxide-mediated metabolic regulation during exercise: Effects of training in health and cardiovascular disease. The FASEB journal. 2000;14:1685–1696.
    1. Stener-Victorin E, Jedel E, Janson PO, Sverrisdottir YB. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comp Physiol. 2009;297:R387–395.
    1. Zoppini G, Cacciatori V, Gemma ML, Moghetti P, Targher G, et al. Effect of moderate aerobic exercise on sympatho-vagal balance in Type 2 diabetic patients. Diabet Med. 2007;24:370–376.
    1. Grassi G, Seravalle G, Calhoun DA, Mancia G. Physical training and baroreceptor control of sympathetic nerve activity in humans. Hypertension. 1994;23:294–301.
    1. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, et al. Effect of Exercise on Coronary Endothelial Function in Patients with Coronary Artery Disease. N Engl J Med. 2000;342:454–460.
    1. Hagg U, Wandt B, Bergstrom G, Volkmann R, Gan L-m. Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults. Am J Physiol Heart Circ Physiol. 2005;289:H1627–1634.
    1. FitzGerald SP, Lamont JV, McConnell RI, Benchikh EO. Development of a High-Throughput Automated Analyzer Using Biochip Array Technology. Clin Chem. 2005;51:1165–1176.
    1. Bonetti PO, Pumper GM, Higano ST, Holmes JDR, Kuvin JT, et al. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. Journal of the American College of Cardiology. 2004;44:2137–2141.
    1. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes. 2007;8:193–198.
    1. Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, et al. Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. Journal of the American College of Cardiology. 2003;41:1761–1768.
    1. Vallbo AB, Hagbarth KE, Torebjork HE, Wallin BG. Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. Physiol Rev. 1979;59:919–957.
    1. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension. 1989;13:647–655.
    1. Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, et al. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol. 1992;453:45–58.
    1. Wallin BG, Thompson JM, Jennings GL, Esler MD. Renal noradrenaline spillover correlates with muscle sympathetic activity in humans. J Physiol 491 (Pt. 1996;3):881–887.
    1. B. Gunnar Wallin NC Sympathetic neural control of integrated cardiovascular function: Insights from measurement of human sympathetic nerve activity. Muscle & Nerve. 2007;36:595–614.
    1. Ng AV, Callister R, Johnson DG, Seals DR. Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension. 1993;21:498–503.
    1. Marsh SA, Coombes JS. Exercise and the endothelial cell. International Journal of Cardiology. 2005;99:165–169.
    1. Morris JNJN. Vigorous exercise in leisure-time: Protection against coronary heart disease. Lancet, The. 1980;2:1207–1210.
    1. Ray CA, Hume KM. Sympathetic neural adaptations to exercise training in humans: insights from microneurography. Med Sci Sports Exerc. 1998;30:387–391.
    1. Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, et al. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. J Clin Invest. 2000;105:1631–1639.
    1. Harada SS. Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circulation research. 1993;72:511–516.
    1. Owlya RR. Cardiovascular and sympathetic effects of nitric oxide inhibition at rest and during static exercise in humans. Circulation. 1997;96:3897–3903.
    1. Zanzinger JJ. Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. Circulation research. 1994;75:1073–1077.
    1. Gao L, Wang W, Liu D, Zucker IH. Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure. Circulation. 2007;115:3095–3102.
    1. Cai H, Harrison DG. Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress. Circ Res. 2000;87:840–844.
    1. Gao L, Wang W, Li Y-L, Schultz HD, Liu D, et al. Superoxide Mediates Sympathoexcitation in Heart Failure: Roles of Angiotensin II and NAD(P)H Oxidase. Circ Res. 2004;95:937–944.
    1. Kojda G, Harrison D. Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. Cardiovascular Research. 1999;43:562–571.
    1. Taniyama Y, Griendling KK. Reactive Oxygen Species in the Vasculature: Molecular and Cellular Mechanisms. Hypertension. 2003;42:1075–1081.
    1. Nohria A, Gerhard-Herman M, Creager MA, Hurley S, Mitra D, et al. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol. 2006;101:545–548.
    1. Sverrisdottir YB, Elam M, Caidahl K, Soderling AS, Herlitz H, et al. The effect of growth hormone (GH) replacement therapy on sympathetic nerve hyperactivity in hypopituitary adults: a double-blind, placebo-controlled, crossover, short-term trial followed by long-term open GH replacement in hypopituitary adults. J Hypertens. 2003;21:1905–1914.
    1. Tsukahara H, Gordienko DV, Tonshoff B, Gelato MC, Goligorsky MS. Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells. Kidney Int. 1994;45:598–604.
    1. Orshal JM, Khalil RA. Gender, sex hormones, and vascular tone. Am J Physiol Regul Integr Comp Physiol. 2004;286:R233–249.
    1. Lowenstein L, Damti A, Pillar G, Shott S, Blumenfeld Z. Evaluation of endothelial function in women with polycystic ovary syndrome. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2007;134:208–212.
    1. Elherik K, Khan F, McLaren M, Kennedy G, Belch JJF. Circadian variation in vascular tone and endothelial cell function in normal males. Clin Sci. 2002;102:547–552.

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