Muscle Sympathetic Nerve Activity Is Related to a Surrogate Marker of Endothelial Function in Healthy Individuals

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/m2) 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.

[1]  E. Stener-Victorin,et al.  Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. , 2009, American journal of physiology. Regulatory, integrative and comparative physiology.

[2]  E. Stener-Victorin,et al.  Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? , 2008, American journal of physiology. Endocrinology and metabolism.

[3]  B. Wallin,et al.  Sympathetic neural control of integrated cardiovascular function: Insights from measurement of human sympathetic nerve activity , 2007, Muscle & nerve.

[4]  S. Shott,et al.  Evaluation of endothelial function in women with polycystic ovary syndrome. , 2007, European journal of obstetrics, gynecology, and reproductive biology.

[5]  D. Theriaque,et al.  Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes , 2007, Pediatric diabetes.

[6]  Lie Gao,et al.  Exercise Training Normalizes Sympathetic Outflow by Central Antioxidant Mechanisms in Rabbits With Pacing-Induced Chronic Heart Failure , 2007, Circulation.

[7]  H. Middlekauff,et al.  Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol , 2007, European journal of heart failure.

[8]  G. Zoppini,et al.  Effect of moderate aerobic exercise on sympatho‐vagal balance in Type 2 diabetic patients , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[9]  Marie Gerhard-Herman,et al.  Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. , 2006, Journal of applied physiology.

[10]  G. Bergström,et al.  Tu-W21:6 Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults , 2006 .

[11]  G. Bergström,et al.  Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults. , 2005, American journal of physiology. Heart and circulatory physiology.

[12]  John V Lamont,et al.  Development of a high-throughput automated analyzer using biochip array technology. , 2005, Clinical chemistry.

[13]  C. Sartori,et al.  Interaction between nitric oxide and the cholinergic and sympathetic nervous system in cardiovascular control in humans. , 2005, Pharmacology & therapeutics.

[14]  J. Coombes,et al.  Exercise and the endothelial cell. , 2005, International journal of cardiology.

[15]  B. Wallin,et al.  Long-term variability and reproducibility of resting human muscle nerve sympathetic activity at rest, as reassessed after a decade , 1993, Clinical Autonomic Research.

[16]  Amir Lerman,et al.  Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. , 2004, Journal of the American College of Cardiology.

[17]  Lie Gao,et al.  Superoxide Mediates Sympathoexcitation in Heart Failure: Roles of Angiotensin II and NAD(P)H Oxidase , 2004, Circulation research.

[18]  V. Somers,et al.  Early Morning Attenuation of Endothelial Function in Healthy Humans , 2004, Circulation.

[19]  C. Morizzo,et al.  Effects of age and physical fitness on microcirculatory function. , 2004, Clinical science.

[20]  R. Khalil,et al.  Gender, sex hormones, and vascular tone. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[21]  K. Griendling,et al.  Reactive oxygen species in the vasculature: molecular and cellular mechanisms. , 2003, Hypertension.

[22]  M. Elam,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 , 2003, Journal of hypertension.

[23]  Amir Lerman,et al.  Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. , 2003, Journal of the American College of Cardiology.

[24]  G. Kennedy,et al.  Circadian variation in vascular tone and endothelial cell function in normal males. , 2002, Clinical science.

[25]  P. Blankestijn,et al.  Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. , 2002, Journal of the American College of Cardiology.

[26]  B. Wallin,et al.  Is the somatotropic axis related to sympathetic nerve activity in healthy ageing men? , 2001, Journal of hypertension.

[27]  G. Berglund,et al.  Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness: Main Results From the &bgr;-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) , 2001, Circulation.

[28]  D. Harrison,et al.  Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. , 2000, Circulation research.

[29]  B. Kingwell.  Nitric oxide‐mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[30]  G. Kojda,et al.  Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. , 2000, The Journal of clinical investigation.

[31]  G. Schuler,et al.  Effect of exercise on coronary endothelial function in patients with coronary artery disease. , 2000, The New England journal of medicine.

[32]  M. Esler,et al.  Sympathetic nervous system activation in essential hypertension, cardiac failure and psychosomatic heart disease. , 2000, Journal of cardiovascular pharmacology.

[33]  G. Kojda,et al.  Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure. , 1999, Cardiovascular research.

[34]  R. Böger.  Nitric oxide and the mediation of the hemodynamic effects of growth hormone in humans. , 1999, Journal of endocrinological investigation.

[35]  P. Chowienczyk,et al.  Evidence for a difference in nitric oxide biosynthesis between healthy women and men. , 1998, Hypertension.

[36]  M. Elam,et al.  Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. , 1998, The Journal of clinical endocrinology and metabolism.

[37]  C. Ray,et al.  Sympathetic neural adaptations to exercise training in humans: insights from microneurography. , 1998, Medicine and science in sports and exercise.

[38]  C. Sartori,et al.  Cardiovascular and sympathetic effects of nitric oxide inhibition at rest and during static exercise in humans. , 1997, Circulation.

[39]  J. Panza.  Endothelial Dysfunction in Essential Hypertension , 1997, Clinical cardiology.

[40]  B. Wallin,et al.  Renal noradrenaline spillover correlates with muscle sympathetic activity in humans. , 1996, The Journal of physiology.

[41]  H. Seller,et al.  Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. , 1994, Circulation research.

[42]  G. Jennings,et al.  Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. , 1994, Journal of the American College of Cardiology.

[43]  G. Mancia,et al.  Physical training and baroreceptor control of sympathetic nerve activity in humans. , 1994, Hypertension.

[44]  B. Tönshoff,et al.  Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells. , 1994, Kidney international.

[45]  R. Ross.  The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[46]  A. Ng,et al.  Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. , 1993, Hypertension.

[47]  A. Takeshita,et al.  Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. , 1993, Circulation research.

[48]  F. Abboud,et al.  Sympathetic-nerve activity during sleep in normal subjects. , 1993, The New England journal of medicine.

[49]  B. Wallin,et al.  Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. , 1992, The Journal of physiology.

[50]  T. Rector,et al.  Endothelium‐Dependent Vasodilation Is Attenuated in Patients With Heart Failure , 1991, Circulation.

[51]  G. Parati,et al.  Comparison of Finger and Intra‐arterial Blood Pressure Monitoring at Rest and During Laboratory Testing , 1989, Hypertension.

[52]  M. Everitt,et al.  VIGOROUS EXERCISE IN LEISURE-TIME: PROTECTION AGAINST CORONARY HEART DISEASE , 1980, The Lancet.

[53]  A. Vallbo,et al.  Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. , 1979, Physiological reviews.

[54]  H. Schumacher,et al.  MITOCHONDRIA IN ONCOGENESIS REVISITED , 1973 .