Proceedings of The Physiological Society

University College Cork (2004) J Physiol 560P, PC4

Communications

ACUTE INTRACEREBROVENTRICULAR (ICV) LEPTIN ADMINISTRATION AND THE BAROREFLEX CONTROL OF RENAL SYMPATHETIC NERVE ACTIVITY (RSNA) IN THE ANAESTHETIZED RAT.

Gaffney,Robert ; Johns,Edward J;

1. Department of Physiology, University College Cork, Cork, Ireland.


Leptin is a hormone secreted by adipose tissue which may have a role in the generation of obesity-induced hypertension. Previous studies have demonstrated that leptin given icv caused a slow increase in sympathetic outflow to a number of organs including the kidney. Moreover, after a period of 3h, Hausberg et al (2002) reported that baroreflex control of RSNA was enhanced. The aim of this study was to evaluate whether an acute increase in brain leptin, that may occur in the post-prandial state, could influence RSNA and the baroreflex. Male Wistar rats, 275-375g, were anaesthetized with ip injection of 1ml of a chloralose/urethane (16.5/250mg/ml) mixture. The right femoral artery and vein were cannulated for recording blood pressure (BP) and heart rate (HR), or giving drugs. The left kidney was exposed and an electrode was sealed onto the renal nerves. Rats were placed in a stereotaxic frame and a guide cannula was implanted into the right lateral cerebral ventricle. The BP and RSNA were measured while BP was manipulated by administration of phenylephrine hydrochloride and sodium nitroprusside (both at 10μg in 0.2ml 154mMol NaCl) before and 20min following leptin infusion (5μg bolus followed by infusion at rate 20μg/h). Animals were killed humanely at end of the experiment. Baroreflex curves for RSNA were analysed using a 4-parameter algorithm as described by Miki et al (2003). Data (means±SEM) were subjected to Student’s t-test and significance taken as p<0.05. Before the leptin infusion, BP was 97± 4 mmHg, HR was 414±15beat/min. The absolute RSNA values varied between animals, therefore to quantify the RSNA response, percentage changes were calculated by taking the mean of the values before the first baroreflex as 100%RSNA. The logistic parameters describing the baroreflex curves for RSNA ie, the range (A1), slope (A2), midpoint BP (A3), and minimum point (A4) were 111.2±6.8%, 0.101±0.008%/mmHg , 114±3mmHg and 13.5±3.3% respectively. Following 20min leptin infusion, while the BP and HR were unchanged, at 97±4mmHg and 409±15beat/min respectively, the RSNA at 149.0±16.5% was significantly increased. Also, while A1 at 134.3±24%, A2 at 0.108±0.01%/mmHg, A3 at 113±4mmHg were stable, A4 at 47.7±14% was significantly increased. The data show that leptin acutely raises the baseline RSNA, which was associated with an increase in A4, but without a significant increase in A1. This suggests that brain leptin can acutely increase baroreflex control of RSNA but does not affect the sensitivity of the baroreflex significantly.

Where applicable, experiments conform with Society ethical requirements