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/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

Physiological and pathophysiological sympathetic nerve hyperactivity. Nerve firing patterns and relation to blood pressure

The sympathetic nervous system plays a crucial role in the development of cardiovascular disease. Sympathetic nerve hyperactivity constitutes an important risk factor for cardiovascular morbidity/mortality. It is therefore of general diagnostic value to be able to identify sympathetic nerve hyperactivity and of major prognostic value to be able to identify early stages of sympatho-excitation.Normal aging and adult hypopituitarism with untreated growth hormone (GH) deficiency are conditions associated with increased cardiovascular morbidity/ mortality. The two conditions share many features, and the physiological somatopaus has been suggested to constitute an age-related GH deficient state. While aging is associated with an increase in sympathetic activity (underlying causes largely unknown) the degree of sympathetic discharge has not been studied in adult GH-deficiency. The microneurographic technique has invaluable advantages over other methods in assessing sympathetic cardiovascular control as it allows direct dynamic intra-neural recordings of postganglionic sympathetic nerve traffic to the muscle vascular bed (MSA). The traditional quantification of MSA is however crude as it only allows evaluation of burst count (frequency (BF) and incidence (BI)) and not absolute burst size (area or amplitude) for individual comparisons. Both measures demonstrate large interindividual variability in healthy humans, which does not constitute a problem in situations of large changes in sympathetic nerve activity which are easily recognised, but is a draw back when it comes to identifying moderate changes in MSA between groups in cross-sectional studies. Hence, the microneurographic technique has, in agreement with norepinephrine kinetic studies, revealed sympathetic nerve hyperactivity in severe forms of hypertension and congestive heart failure. However, whether milder forms of heart failure and hypertension are conditions associated with sympathetic activation remains a matter of controversy.In the present studies we evaluated the sympathetic nervous systems relationship to changes in the GH/IGF-I axis as well as the role of MSA in the control of blood pressure level. We also evaluated whether the distribution of burst amplitudes would provide a more sensitive indicator of altered MSA by comparing known and assumed sympatho-excited conditions of different genesis. Resting MSA was recorded and analysed in patients with 1) varying degrees of cardiac failure, prior to and following cardiac transplantation (HTx), 2) hypopituitarism and untreated growth hormone (GH) deficiency and 3) in several groups of healthy controls including a large group of healthy men with a wide age range.MSA BF, BI and proportion of large amplitude bursts increased with the degree of cardiac failure and were normalised following HTx. Furthermore the amplitude distribution was able to identify altered MSA in mild cardiac failure where traditional burst counts failed. MSA BF and BI were also markedly augmented in GH deficient patients and with increasing age whereas in these conditions the burst amplitude distribution was unaffected. MSA was found to be inversely correlated to serum IGF-I concentrations and positively related to diastolic blood pressure levels both in the GH deficient patient group and aging healthy group. MSA was also shown to be an independent predictor of blood pressure level though its influence was much less than that of body mass index.We conclude that the decline in the GH/IGF-I axis seen in GH deficiency and with increasing age is coupled to the increase in MSA which contributes to the blood pressure rise and cardiovascular risk factors associated with the two conditions and that the distribution of burst amplitudes provides a more sensitive indicator of altered MSA in mild CHF, capable of discriminating between sympatho-excitation of different genesi

Simple correlation matrix showing associations between Muscle Sympathetic Nerve Activity (MSNA), Reactive Hyperemic Index (RHI), Platelet concentration (PLT), Epidermal growth factor (EGF), Insulin-Like Growth Factor (IGF)-I, and physical activity (PA) for the study group.

<p><i>P</i>-values are indicated as: *<i>p</i>≤0.05; **<i>p</i>≤0.01; ***<i>p</i>≤0.005.</p

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.

<p>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.</p

Basic characteristics of the 10 (7 M/3 F) subjects shown in mean, SD and range.

<p>Basic characteristics of the 10 (7 M/3 F) subjects shown in mean, SD and range.</p

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).

<p>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).</p