Conference Publication Details
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Buckley, M Brennan, D and Johns, E;
Physiological Society General Meeting
Renal excretory responses to a volume load in conscious Wistar rats with heart hypertrophy
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Heart hypertrophy is considered to be an initial indicator of a progression into heart failure which is accompanied by an activation of the autonomic nervous system to maintain cardiac output. We reported (Flanagan et al., 2008) in anaesthetised rats that an acute volume expansion decreased renal sympathetic nerve activity (RSNA) and that this reflex was absent in rats with heart hypertrophy after isoprenaline/caffeine or thyroxine administration. At the kidney, this raised level of RSNA would cause fluid retention exacerbating the load on the heart. This study examined whether in conscious rats the ability to excrete a volume load was altered in any way in heart hypertrophy. A further objective was to examine how these responses were altered following denervation of the kidneys. Two groups of Wistar rats (n=6) were used, one intact and the other subjected to a bilateral renal denervation 1 week previously. The animals were anaesthetised (3% isoflurane in O2) and each kidney in turn was exposed via a flank incision, all fat and connective tissue stripped from around the renal artery which was then bathed with 10% phenol in ethanol for 1 min, rinsed with saline and then muscle and skin sutured. Tail vein blood samples were obtained under brief isoflurane anaesthesia and a 24h urine collection taken. On day 1 at 10.00 am, animals received an oral gavage of tap water (2ml/100g body weight) and urine samples were collected every 2h for 6h. Thereafter, the rats received isoprenaline (5mg/kg) every 72 h for 2 weeks and drinking water containing caffeine (61.5mg/kg). At week 1 and 2, tail vein sampling, oral gavage and urine collection was repeated. Creatinine clearance (glomerular filtration rate, GFR), urine volume (UV) and absolute sodium excretion (UNaV) were determined. Data, means ▒ S.E.M. were taken as significant when P<0.05 (ANOVA) The intact rats had a basal GFR of 1.73▒0.25ml/min/kg, UNaV of 0.52▒0.1μmol/min/kg and UV of 22.8▒3.08Ál/min/kg which were unchanged at weeks 1 and 2. The water load in intact rats caused cumulative increases in UV, from 3.5▒0.22ml at 2h to 5.3▒0.21ml 6h, and in UNaV from 1.98▒0.26μmol/min/kg at 2h to 16.48▒3.87μmol/min/kg at 6h. At week 2 the magnitude of the cumulative increases in UV and UNaV were reduced (both P<0.05) by some 60%. In the rats subjected to bilateral renal denervation, the water load resulted in a cumulative rise in UV, from 3.26▒0.30ml at 2h to 5.96▒0.22ml at 6h, and UNaV from 1.6▒0.25μmol/min/kg over 2h to 7.11▒0.74 μmol/min/kg at 6h, responses similar to those obtained in the intact rats. The magnitude of the increases in UV and UNaV after the water load were unchanged after the 2 weeks of isoprenaline/caffeine treatment in the renally denervated group which was different from the intact group (P<0.05). These findings demonstrated that in the isoprenaline/caffeine model of heart hypertrophy there was a blunted ability to excrete a volume load, which was most likely due to a lack of suppression of RSNA as the excretory response was unchanged following renal denervation. Exactly how the cardiopulmonary receptor sensitivity changes in heart hypertrophy remains to be explored.
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