Temporal development of baroreceptor dysfunction in a rodent model of chronic kidney disease.

Altered autonomic control of the cardiovascular system in chronic kidney disease (CKD) contributes to an increased risk of cardiovascular events. The aim of the present study was to determine whether and when autonomic dysfunction occurs in a conscious, telemetered, rodent model of CKD. In Lewis polycystic kidney (LPK; n = 8) and Lewis (n = 8) rats, blood pressure (BP), heart rate (HR), HR variability (HRV), systolic BP variability (SBPV) and baroreflex sensitivity (BRS) were determined from 10 to 16 weeks of age. The LPK rats had higher systolic BP (average across all ages: 230 ± 10 vs 122.6 ± 0.3 mmHg; P < 0.001), increased SBPV (average across all ages: 13.9 ± 1.9 vs 5.2 ± 0.2 mmHg(2) ; P < 0.01) and reduced low-frequency HRV power (average across all ages: 1.5 ± 0.3 vs 2.6 ± 0.2 msec(2) ; P < 0.05). Between 10 and 12 weeks of age, SBPV increased twofold in the LPK rat (8.13 ± 1.05 vs 16.10 ± 1.31 mmHg(2) for 10 vs 12 weeks of age, respectively; P < 0.001), coinciding with an approximate 40% reduction in BRS (1.32 ± 0.14 vs 0.79 ± 0.11 ms/mmHg for 10 vs 12 weeks of age, respectively; P < 0.05). There was no difference in BRS between LPK and Lewis rats at 10 weeks of age; however, from 12 weeks onwards, BRS was reduced in LPK rats (0.75 ± 0.01 vs 1.17 ± 0.04 ms/mmHg; P < 0.01). Baroreceptor regulation of HR becomes impaired between 10 and 12 weeks of age in the LPK rat, coinciding with an increase in SBPV. Preventing baroreflex dysfunction in CKD may reduce SBPV and the associated mortality risks.

Effect of anaesthetic and choice of neuromuscular blocker on vagal control of heart rate under laboratory animal experimental conditions.

Neuromuscular-blocking agents are commonly used in laboratory animal research settings. Due to actions of cholinergic receptors at locations other than the motor end-plate, these agents have a strong propensity to modulate autonomic outflow and may therefore not be desirable in studies examining autonomic function. This study aimed to compare the effect of two non-depolarizing neuromuscular-blocking agents, pancuronium and cisatracurium, on blood pressure, heart rate and non-invasive indices of autonomic function (heart rate variability, systolic blood pressure variability and baroreflex sensitivity) under two different types of anaesthesia in Lewis rats. Pancuronium produced a profound vagolytic response characterized by tachycardia, reduction in heart rate variability and baroreflex sensitivity under urethane anaesthesia, and with minimal effect under isoflurane anaesthesia. Conversely, cisatracurium produced no evidence of vagolytic action under either urethane or isoflurane anaesthesia. Therefore, for studies interested in examining autonomic function, particularly baroreflex or vagal function, neuromuscular blockade would be best achieved using cisatracurium.