Cardiovascular autonomic dysfunction in a novel rodent model of polycystic kidney disease

• Published in: Autonomic neuroscience 2010-01, Vol.152 (1), p.60-66
• Main Authors: Harrison, Joanne L, Hildreth, Cara M, Callahan, Stephen M, Goodchild, Ann K, Phillips, Jacqueline K
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Antihypertensive Agents - pharmacology; Atenolol - pharmacology; Atropine Derivatives - pharmacology; Autonomic Nervous System - physiopathology; Baroreflex - drug effects; Baroreflex - physiology; Baroreflex function; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular System - innervation; Cardiovascular System - physiopathology; Disease Models, Animal; Electrophysiologic Techniques, Cardiac - methods; Fourier Analysis; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Heart rate variability; Hypertension; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical Education; Nitroprusside - pharmacology; Parasympathetic; Parasympatholytics - pharmacology; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Polycystic Kidney, Autosomal Recessive - physiopathology; Rats; Rats, Inbred Lew; Signal Processing, Computer-Assisted; Sympathetic; Vertebrates: nervous system and sense organs
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2009.09.019

Abstract 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.