Cardiac autonomic dysfunction in chronic kidney disease

Background Chronic kidney disease is associated with altered autonomic control of the cardiovascular system. We have shown previously that sympathovagal control of heart rate (HR) is perturbed in the Lewis Polycystic Kidney (LPK) rat under anaesthetised conditions(1). We aimed to determine if comparable changes are evident in conscious telemetered rats. Methods Telemetry probes were implanted in 5-week old, mixed-sex LPK (n = 8) and Lewis controls (n = 9). Circadian rhythms of HR and mean arterial blood pressure (MAP) were recorded from 6-16 weeks of age and changes in HR in response to atenolol (1mg/kg i.p) and methylatropine (2mg/kg i.p) were determined fortnightly to assess sympathetic and parasympathetic contributions, respectively. Results Across all ages studied LPK showed marked hypertension during both dark and light cycles (MAP: 190.9 ± 4.7 and 189.0 ± 5.9 mmHg, respectively). 24hr circadian rhythms showed an age related decline in HR for both strains (p < 0.001). During the light cycle, HR was higher in LPK than Lewis (374.9 ± 9.2, vs. 347.6 ± 8.0 bpm, p < 0.05). After atenolol, the decrease in HR from resting was greater in LPK than Lewis (-88.6 ± 18.5 vs. -47.2 ± 6.1 mmHg, p < 0.05). After methylatropine, the increase in HR was less in the LPK (31.5 ± 8.1 vs. 77.1 ± 11.2, p < 0.05). Intrinsic HR, as determined after atenolol and methylatropine, was not different between the two strains. Conclusions This data confirms our previous findings that LPK have anelevated resting HR due to both increased sympathetic and reduced vagal inputs to the heart, and that cardiac autonomic dysfunction should be an important treatment consideration.