Respiratory Modulation Of Sympathetic Nerve Activity Research Articles

Aging in females is associated with changes in respiratory modulation of sympathetic nerve activity and blood pressure.

Sympathetic nerve activity (SNA) is tightly coupled with the respiratory cycle. In healthy human males, respiratory modulation of SNA does not change with age. However, it is unclear how this modulation is affected by age in females. We investigated whether respiratory sympathetic modulation is altered in healthy postmenopausal (PMF) versus premenopausal female (YF), and younger male (YM) adults, and determined its relationship to resting blood pressure. Muscle SNA (MSNA; microneurography), respiration (transducer belt), ECG, and continuous blood pressure were measured in 12 YF, 13 PMF, and 12 YM healthy volunteers. Respiratory modulation of MSNA was quantified during two phases of the respiratory cycle: mid-late expiration and inspiration/postinspiration. All groups showed respiratory modulation of MSNA (P < 0.0005). There was an interaction between the respiratory phase and group for MSNA [bursts/100 heartbeats (HB) (P = 0.004) and bursts/min (P = 0.029)], with smaller reductions in MSNA during inspiration observed in PMF versus the other groups. Respiratory modulation of blood pressure was also reduced in PMF versus YF (6 [2] vs. 12 [9] mmHg, P = 0.008) and YM (13 [13] mmHg, P = 0.001, median [interquartile range]). The magnitude of respiratory sympathetic modulation was related to resting blood pressure in PMF only, such that individuals with less modulation had greater resting blood pressure. The data indicate that aging in postmenopausal females is associated with less inspiratory inhibition of MSNA. This correlated with a higher resting blood pressure in PMF only. Thus, the reduced modulation of MSNA could contribute to the age-related rise in blood pressure that occurs in females.NEW & NOTEWORTHY The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation.

Chapter 1 - Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states.

Respiratory‐Sympathetic Interactions and Central Baroreflex Pathways: Insights from Computational Modeling

The sympathetic nerve activity (SNA) is modulated by respiratory activity which indicates the existence of direct interactions between the respiratory and sympathetic networks within the brainstem. Our experimental studies reveal the respiratory phase- and pontine-dependent effects of baroreceptor stimulation on both the respiratory pattern and the respiratory modulation of SNA. This suggests that the sympathetic baroreceptor reflex has two central pathways: one is independent of the respiratory-sympathetic interactions, and the other operates via the respiratory pattern generator and is dependent on the respiratory modulation of SNA. Our experimental studies in the perfused in situ rat preparation and complementary computational modeling studies support the hypothesis that baroreceptor activation during expiration prolongs the expiratory phase via activation of the post-inspiratory neurons of the Bötzinger Complex. Further, these neurons are critically involved in the respiratory modulation of SNA and mediate an additional central pathway of the sympathetic baroreceptor reflex. Supported by: NIH (R01 NS057815, R33 HL087379, R01 NS069220).

Effect of baroreceptor stimulation on the respiratory pattern: Insights into respiratory–sympathetic interactions

Sympathetic nerve activity (SNA) is modulated by respiratory activity which indicates the existence of direct interactions between the respiratory and sympathetic networks within the brainstem. Our experimental studies reveal that T(E) prolongation evoked by baroreceptor stimulation varies with respiratory phase and depends on the pons. We speculate that the sympathetic baroreceptor reflex, providing negative feedback from baroreceptors to the rostral ventrolateral medulla and SNA, has two pathways: one direct and independent of the respiratory-sympathetic interactions and the other operating via the respiratory pattern generator and is hence dependent on the respiratory modulation of SNA. Our experimental studies in the perfused in situ rat preparation and complementary computational modelling studies support the hypothesis that baroreceptor activation during expiration prolongs the T(E) via transient activation of post-inspiratory and inhibition of augmenting expiratory neurones of the Bötzinger Complex (BötC). We propose that these BötC neurones are also involved in the respiratory modulation of SNA, and contribute to the respiratory modulation of the sympathetic baroreceptor reflex.

Elevated sympathetic activity precedes the arterial hypertension in the Goldblatt model

Despite the extensive use of the Goldblatt model of hypertension (two kidney one clip, 2K1C) sympathetic mechanisms responsible for both the development and maintenance of the elevated blood pressure remain unclear. We tested the hypothesis that sympathetic nerve activity (SNA) is elevated by the third week after clipping and before development of hypertension. Using the in situ working heart brainstem preparation, male Wistar rats were divided into three groups: Sham (n=7), and 2K1C (3 weeks) of which some were hypertensive (2K1C‐H, n=6) or and others normotensive (2K1C‐N, n=9) as determined a priori. At comparable perfusion rates, pressures were higher in both 2K1C groups (2K1C‐H: 76 ± 1; 2K1C‐N: 74 ± 3 vs Sham: 60 ± 2 mmHg, p&lt; 0.05). The respiratory modulation of SNA was significantly elevated in both 2K‐1C groups (e.g. 2K1C‐H: 47.7 ± 6.1; 2K1C‐N: 32.8 ± 2.8 vs Sham: 20.5 ± 2.5 μV, p&lt; 0.05). Pre‐collicular transection reduced SNA in all rat groups (2K1C‐H: 32.5 ± 7.5, 2K1C‐NH: 48 ± 6.9 vs Sham: 13.2 ± 1%, p&lt; 0.05). Subsequent transection at the medullary‐spinal cord abolished SNA in Sham and 2K1C‐N but decreased it by 57± 5.5% in 2K1C‐H. We conclude, SNA can be raised prior to onset of hypertension by the 3rd week after clipping and this, in part, originates from enhanced respiratory modulation. Supported by CAPES and British Heart Foundation.