The worldwide increase in obesity is dramatic and the World Health Organisation has called obesity a global epidemic. There is a close association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the kidneys. Renal sympathetic nerve activity is particularly important since it affects salt and water balance directly and indirectly by influencing renin release from the kidney. The regulation of renal function by the sympathetic nerves is a key player in obesity induced hypertension. The causes of the elevated sympathetic nerve activity observed in obesity are not well understood but leptin makes an important contribution. The adipokines, leptin and resistin, which are secreted from adipose tissue, act in the brain and are important in regulating metabolic and cardiovascular functions. In this study we investigated the effects of acute central administration of leptin and resistin, alone and in combination, on renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in anaesthetised Sprague-Dawley male rats (442+12 gm). Under general anaesthesia (isofluorane 2-3% in oxygen), the femoral vein and artery were cannulated to allow anaesthesia to be maintained with urethane (1.4-1.6 g/kg iv, followed by supplemental doses of 0.05 g/kg as required) and blood pressure recording, respectively. The left renal nerve was identified and placed onto bipolar electrodes for recording of RSNA. MAP, HR and RSNA were recorded before and for 3 hours after intraventricular saline (n=4), leptin (7 µg; n=5), resistin (7 µg; n=4) and the combination of both resistin + leptin (n=6) (leptin was administered 15 minutes after resistin). Data are mean + SEM and compared by ANOVA. Leptin alone increased RSNA by a maximum of 74+17% and resistin alone increased RSNA by 50+14%, (P<0.05 from saline). When resistin + Leptin were administered there was a greater increase in RSNA (maximum increase=163+23%; P<0.05, compared to the responses to either drug alone). Changes in MAP and HR from pre-drug levels were not different between groups. The findings show that the combination of both leptin and resistin leads to significantly greater increases in RSNA, suggesting an enhanced effect. Since leptin makes an important contribution to the elevated RSNA observed in obese and overweight conditions, the presence of increased leptin and resistin levels may mean the contribution of leptin to the increased RSNA in those conditions is enhanced.
Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, C60
Oral Communications: Regulation of renal sympathetic nerve activity by leptin and resistin
E. Badoer1,2, H. Habeeballah1,2, N. Alsuhaymi1,2, M. Stebbing1,2
1. School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia. 2. Health Innovations Research Institute, RMIT University, Melbourne, Victoria, Australia.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.