Cardiovascular autonomic dysfunction in a novel rodent model of polycystic kidney disease
Harrison, J.L., Hildreth, C.M., Callahan, S., Goodchild, A.K. and Phillips, J.K. (2010) Cardiovascular autonomic dysfunction in a novel rodent model of polycystic kidney disease. Autonomic Neuroscience, 152 (1-2). pp. 60-66.
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Autonomic dysfunction, hypertension and cardiovascular morbidity in end stage renal disease are critically linked, however there are limited models available to investigate this relationship and develop clinical interventions. This study aimed to define the relationship between hypertension and autonomic function in a new rodent model of polycystic kidney disease (PKD). Using measures of heart rate and systolic blood pressure variability (HRV, SBPV), and time domain analysis of cardiac and sympathetic baroreflex function, we compared the Lewis PKD model (LPK) to a Lewis control. Systolic BP and SBPV were significantly higher in LPK vs. Lewis (168 ± 7 vs. 131 ± 8 mm Hg, P ≤ 0.01, total power: 11 ± 3.1 vs. 1.3 ± 0.3 mm Hg/Hz2, P ≤ 0.05). LPK has a higher resting HR (437 ± 17 vs. 330 ± 11 beats per minute [bpm], P ≤ 0.001) associated with reduced HRV (total power [1.7 ± 0.3 vs. 4.6 ± 1.1 ms/Hz2, P ≤ 0.01]). Atenolol decreased HR to a greater extent in the LPK (90 ± 10 vs. 20 ± 17 bpm, P ≤ 0.001) while subsequent methylatropine administration produced a greater increase in Lewis HR (24 ± 9 vs. 66 ± 9 bpm, P ≤ 0.01). No difference in intrinsic HR following both drugs existed. Cardiac baroreflex function was impaired in LPK vs. Lewis (0.6 ± 0.4 vs. 1.2 ± 0.2 bpm/mm Hg P ≤ 0.05, and 0.3 ± 0.1 vs. 3.1 ± 0.6 ms/mm Hg, P ≤ 0.001, respectively). The sympathetic baroreflex function curve was shifted upwards and towards the right in LPK (P ≤ 0.01). Sympathetic baroreflex gain was not altered. This data suggests that sympathetic hyperactivity and reduced vagal function underlies the hypertension and reduced cardiac baroreflex function in the LPK model.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Integrated Health Institute|
School of Veterinary and Biomedical Sciences
|Copyright:||© 2009 Elsevier B.V.|
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