Gamma melanocyte hormone(γ-MSH) has been shown to induce natriuresis in the rat[1],is this affect augmented in rats exposed to a high salt diet? Male Wistar rats were fed either a normal salt chow(0.4% Harlan Tecklad) or high salt diet(4% NaCl Lillico® Biotechnology) for 3 weeks ad libitum. For γ-MSH infusion studies (n=6) male Wistar rats were anaesthetised using urethane/chloralose 4ml/kg i.p. The right femoral vein and artery were cannulated for blood pressure and heart rate recordings and for saline and FITC-inulin infusion.Kidneys were exposed using flank incisions and the ureters cannulated. Right kidneys were cannulated into the medullary-cortex boundary and infused at 1ml/hour with either vehicle or γ-MSH at 500fmol/min.The left kidney acted as control for each rat. Renal blood flow to the infused kidney was monitored by an ultra sonic flow probe, attached to the right renal artery. A significant p>0.05 (t-test) increase in blood pressure and heart rate was noted during peptide infusion, which returned to baseline levels following cessation of the infusion. UNaV increased by 70% and %FEV increased by 46% in the infused kidney as compared to the contralateral control kidney p<0.001. There were no associated changes in GFR. For isolated cell studies, 3 male rats were anaesthetised as for functional experiments and the kidneys extracted via flank incisions. Kidneys were maintained in ice cold media prior to dissection. Papillae and medulla were dissected with the aid of a chilled dissecting microscope. The tissue obtained, was incubated in 1mg/ml collagenase for 1 hour at 37^○C, papilla and medullary cells were harvested by isotonic shock lysis to give pure collecting duct cells. Western blot/densitometric analysis on freshly isolated cells indicates that in rats fed a high salt diet for 14 days, there was a 20 fold increase in expression of MC3R in inner medullary/papillary collecting duct cells compared to inner medullary/papillary collecting duct cells from rats fed a normal salt diet(P >0.01, t-test. n=3). Following in vitro treatment of inner medullary/papillary collecting duct cells from high salt and normal salt fed rats (14 days) with 2 mM NDP γ-MSH for 15 min there was a 6 fold increase in cAMP production in cells isolated from high salt fed rats compared to cells isolated from normal salt fed rats (P >0.05, t-test. n=3). The associated parallel increases in cAMP production concurrent with MC3R activation confirm salt responsive upregulation of MC3 receptor activity. The natriuretic response can therefore be induced by the infusion of γ-MSH and is one method of regulating osmolality and plasma sodium concentration in rats chronically fed a high salt diet. This system may be an important target to modulate in those with salt-sensitive hypertension.