Maturation-related changes in the pattern of renal sympathetic nerve activity from fetal life to adulthood

Abstract

Sympathetic nerve activity (SNA) has two main properties, the presence of co-ordinated bursts of activity, indicative of many nerve fibres firing at a similar time, and entrainment of the bursts to the cardiac cycle, due to inhibitory input from baroreceptors to a network of cell groups within the CNS. Although this patterning is used as a 'gold standard' for the identification of successful nerve recordings, the maturation of these basic features of SNA from fetal life to adulthood has not been investigated. Using a telemetry-based nerve amplifier, renal SNA (RSNA) was recorded in preterm (99 ± 1 days gestation; term 147 days) and near-term fetal sheep (119 ± 0 days gestation), without anaesthesia or paralysis, and contrasted with RSNA recorded in adult sheep. All three age groups showed a classic bursting pattern of RSNA and co-ordination of bursts with the cardiac cycle. However, the delay between diastole and the next peak in RSNA was longest in preterm fetuses (319 ± 1 ms), compared with near-term fetuses (250 ± 13 ms), and shortest in the adult sheep (174 ± 38 ms). This was independent of the maturational decrease in heart rate. The near-term fetuses showed a marked but sleep-statedependent increase in resting RSNA compared with preterm fetuses. Although entrainment with the pressure pulse suggests that the intricate circuitry within the CNS is developed in the preterm fetus, the decrease in the length of the delay suggests continuing maturation of this key feature of RSNA in the last third of gestation and after birth. The sympathetic nervous system (SNS) plays a vital role in cardiovascular, metabolic and thermoregulatory homeostasis. Direct recording of sympathetic nerve activity (SNA) allows continuous assessment of changes in the SNS in response to various stimuli. Since the early recordings of SNA, a number of distinct features have been identified. Firstly, SNA has a co-ordinated bursting pattern as a result of synchronized firing of many individual neurons at approximately the same time and secondly, the bursts of nerve activity display a number of rhythmicities, in particular, synchronization with the heart rate (Adrian & Bronk, 1932;Bronk et al. 1936;Malpas, 1998Malpas, , 2010.Previous studies have quantified this cardiac-related rhythm as the delay between diastole and the following peak in SNA, reporting delays of 164 ± 7 ms in adult cats (cardiac SNA;Hedman et al. 1994) and 105 ± 7 ms in renal SNA (RSNA) in adult rabbits (Barrett et al. 2003). The presence of entrainment of RSNA to the cardiac cycle is indicative of the delicate control of efferent nerve activity and is often regarded as a 'gold standard' for the identification of successful nerve recordings. Indeed, in early descriptions of RSNA in near-term fetal sheep, the activity was described as being pulse synchronous; however, this relationship was not quantified (Smith et al. 1990;Segar et al. 1998).We have recently shown that preterm fetal sheep have co-ordinated bursts of RSNA that are entrained to the cardiac cycle ). However, the ...

Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

“…Both systems are active in late gestation, and influence both basal cardiovascular function and sleep state-related changes (Zhu & Szeto, 1987;Wakatsuki et al 1992;Jensen et al 2009). There is strong direct and indirect evidence for further maturation of the SNS (Segar et al 1992;Wakatsuki et al 1992;Booth et al 2011) and PNS in the last third of gestation (Nuwayhid et al 1975;Assali et al 1977;Walker et al 1978). The known progressive fall in fetal heart rate (FHR) with age is broadly consistent with clinical studies that suggest a general trend for LF/HF to decrease with gestational age (ga; Chatow et al 1995;Van Leeuwen et al 2003;David et al 2007).…”

“…Nevertheless, it is reasonable to consider that there was also no significant differential effect of 6-OHDA between sleep states on the power spectra. We found apparent trends for increased LF/HF during the atropine infusion and a reduction after sympathectomy that would be consistent with higher basal parasympathetic tone in LV sleep and sympathetic tone in HV sleep (Baust & Bohnert, 1969;Booth et al 2011). The most likely explanation for this apparent lack of effect is simply a combination of the considerable within-and between-subject variation in measurements, and the fact that the study was not large enough to detect these effects, given the multiple variables that affected fetal HRV (treatment, frequency band and sleep state).…”

“…By late gestation, distinct fetal sleep states are well established, with a pattern of greater cardiac sympathetic tone during the HV state (Zhu & Szeto, 1987;Walker et al 1990;Wakatsuki et al 1992;Booth et al 2011) and greater vagal tone during the LV state (Walker et al 1990;Wakatsuki et al 1992;Jensen et al 2009). In the present study, we found that FHR and VLF activity increased in HV sleep compared with LV sleep, with a corresponding increase in the LF/HF ratio.…”

Reinnervation of Renal Afferent and Efferent Nerves at 5.5 and 11 Months After Catheter-Based Radiofrequency Renal Denervation In Sheep

“…26,27 Intrapelvic infusion of capsaicin (1 µg/1 mL for 1 minute) had no significant effects on MAP, HR or RSNA, with a trend toward a small increase in RBF (−6±3 mL/min; P<0.09). In view of this lack of treatment effect this was not repeated in the other groups.…”

Preterm Birth and Hypertension Risk

“…60 Sympathetic nerve activity contributes to blood pressure maintenance, to the elevation in blood pressure in situations of overactivation (or impaired counterregulatory mechanisms) in many forms of chronic hypertension, and after deleterious perinatal conditions (such as IUGR) in both humans and experimental models. [61][62][63] Sympathetic nerve activity can also be activated by chronic inflammation (including through inflammatory cytokines secreted by adipose tissue) and increased expression of the RAS.…”