Acta Pharmacologica Sinica (2010) 31: 145–149; doi: 10.1038/aps.2009.179; published online 21 December 2009

¹Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing 210029, China; ²National Drug Screen Laboratory, China Pharmaceutical University, Nanjing 210009, China; ³Department of Physiology, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China

Aim: To investigate the possible role of hypothalamic kisspeptin in the regulation of body fluid metabolism and maintenance of internal homeostasis. 

Methods: Natriuresis and diuresis were induced by blood volume expansion (VE) in anesthetized male rats and kisspeptin-10 was  intracerebroventricularly (icv) administered.  Radioimmunoassay (RIA) was used to measure the plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations during the VE.  The mediation of the renal sympathetic nerve was also investigated in rats with bilateral renal sympathetic denervation.

Results: The increased urine flow and sodium excretion induced by VE were significantly inhibited by icv injection of 5 nmol kisspeptin-10 (P<0.05), which peaked 20 min after the decrease in VE.  The mean arterial blood pressure and heart rate did not change during the experiment.  Plasma AVP concentrations were significantly increased 20 min after icv injection of 5 nmol kisspeptin-10 during VE (P<0.05), while pretreatment with 5 nmol kisspeptin-10 did not significantly change plasma ANP concentrations.  Furthermore, pretreatment with 5 nmol kisspeptin-10 could significantly inhibit VE-induced natriuresis and diuresis in renal sympathetic denervated rats (P<0.05).

Conclusion: Central administration of kisspeptin-10 inhibited VE-induced natriuresis and diuresis.  This effect was likely mediated by increasing AVP release independent of plasma ANP concentration and renal sympathetic nerve activity. 

Keywords: kisspeptin; natriuresis; diuresis; volume expansion; hypothalamus