INTRODUCTION. Glucocorticoid (GC) excess causes hypertension and cardiovascular disease (1). Renal mineralocorticoid and glucocorticoid receptors (MR & GR) regulate Na+ excretion and thence blood pressure (BP). The renin-angiotensinogen-aldosterone system (RAAS) activates MR, while the hypothalamic-pituitary-adrenal axis activates GR. However, these systems are not separate entities; signal crosstalk may occur at several stages including at receptor level (2). Renal GR & MR activity is tuned by intra-renal 11β-Hydroxysteroid Dehydrogenases (11βHSDs), which modulate GC concentrations. The kidney expresses both 11βHSD isoforms. While 11βHSD type 2 (inactivation of cortisol) has an established role as the protector distal nephron aldosterone sensitivity, the function of renal 11βHSD type 1 (reactivation of cortisol) is unknown (3). This study explores the effect of 11βHSD1 deletion on renal function. We hypothesise that 11βHSD1 promotes GC activity and anti-natriuresis thereby supporting BP (2). METHODS. All studies were conducted in age-matched male C57BL/6J mice: wild-type (WT) or global 11βHSD1 knockout (HSD1-/-). Mice were housed in metabolism cages (N=22) and fed 0.2% Na+ diet for 4 days and 2.1% Na+ diet for 8 days. Data were normalised, tested for normality, analysed by ANOVA and presented as F- and p-values of genotype (GT), salt intake (SI) and interaction (IA), respectively. Urinary steroid excretion (N=6) was analysed by ELISA (4). Plasma RAAS-parameters (N≥26) were measured by RIA (5).RESULTS. There was no difference in Na+ intake between HSD1-/- and WT mice (IA: F=1.66, p=ns; GT: F=0.74, p=ns). Genotype did not affect water balance (IA: F=1.49, p=ns; GT F=0.01, p=ns) or Na+ balance (IA: F=0.66, p=ns; GT F=0.25, p=ns). High Na+ diet increased corticosterone excretion 3-fold, but there were no differences between GTs (IA F=1.14, p=ns; GT F=0.10 p=ns; SI F=3.47, p<0.05). HSD1-/- mice had a 2.5-fold greater excretion of deoxycorticosterone (DOC) during high Na+ intake (IA F=3.00, p<0.05; GT F=4.40 p=ns; SI F=10.74, p<0.001). Plasma renin and angiotensinogen (AGT) concentrations were appropriately down regulated by high Na+ intake in both GTs (Renin: IA F=1.45, p=ns; GT F=1.36 p=ns; SI F=23.39, p<0.001) (AGT: IA F=0.19, p=ns; GT F=1.59, p=ns; SI F=6.09, p<0.05). The urinary excretion of nitric oxide metabolites (N=6) increased 80% during high Na+ intake with no difference between GTs (IA F=0.69, p=ns; GT F=0.06, p=ns; SI F=14.50, p<0.001). SUMMARY. Steroid (i.e. DOC) homeostasis was disrupted in HSD1-/- mice, but there was no significant effect on renal water/Na+ excretion. We hypothesise that such an effect may be masked by counter-regulatory changes in the neurohormonal controllers of Na+ excretion. Our future work is directed at unravelling the underlying mechanisms.