Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, PC165

Communications

Baroreflex regulation of renal sympathetic nerve activity in anaesthetised rats with heart damage.

Flanagan, Evelyn ; johns, edward James;

1. Physiology, University College Cork, cork, Ireland.


In man and in animal models of heart failure, there is activation of the sympathetic nervous system (SNS) to increase cardiac output to meet the metabolic demands of the body. There is evidence from animal models using coronary artery ligation induced heart failure, that there is a derangement in the arterial baroreceptor regulation of the SNS. A less well investigated model is the high output model, using ateriovenous fistulae or catecholamine administration, to produce an increase in cardiac output leading to ventricular damage (Leenen et al, 2001). This study aimed to determine whether the baroreflex regulation of renal sympathetic nerve activity (RSNA) was deficient in a rat model of catecholamine mediated cardiac damage. All experiments accorded with current European legislation. Male Wistar rats, 180-240g, were kept for 2 weeks on a regular diet and given either tap water to drink or water containing caffeine (at a concentration to deliver 80mg/kg/day) plus sc isoprenaline (1mg/100g) every 72h. The animals were anaesthetised, 1ml chloralose/urethane (16.5/250mg/ml) ip, and prepared for recording activity in the sympathetic nerves to the left kidney. Phenylephrine and nitroprusside, each of 10 μg, were given iv over 40s to increase and decrease blood pressure, respectively and the changes in RSNA and heart rate were used to generate baroreflex curves (Kent et al, 1972). The animals were killed using an anaesthetic overdose. Means ± SEM were subjected to the Students ‘t’ test and significance taken when P<0.05. The rats given water to drink increased body weight from 180±10 to 231±8 g which was greater (P<0.05) than in rats given caffeine and isoprenaline (207±5 to 240±9g). In the acute study, basal blood pressure was 103±2 mmHg in the control rats but was slightly lower, at 94±4 mmHg in the caffeine/isoprenaline treated rats. The range of the baroreflex curve (A1) for RSNA was similar in both control and experimental groups of rats, 93±2 versus 97±1μV/s but the slope (A2) was lower in the experimental group (0.14±0.01 versus 0.20±0.05 μV/s/mmHg, P<0.05) as was the mid point blood pressure (115±2 versus 100±3 mmHg, P<0.05). By contrast, A4, the range of RSNA, was greater in the experimental than control groups (54±8 versus 33±2, μV/s, P<0.05). These data show that in this model of catecholamine induced heart damage, the animals grow more slowly, and there is a depression in the sensitivity of the baroreflex regulation of RSNA. Whether this defect in baroreflex control resides in the afferent, central or efferent limbs of the reflex remains to be resolved.

Where applicable, experiments conform with Society ethical requirements