The epithelial Na⁺ channel (ENaC) is a regulated pathway for Na⁺ uptake across the luminal membrane of the renal collecting duct (CD) and plays an important role in blood pressure control. Activation of many P2 receptor (P2R) subtypes (including: P2X_{2, 4, 2/6 and/or 4/6} and P2Y_{2 and/or 4}) expressed in CD epithelial cells can alter ENaC activity in different ways (Wildman et al. 2005, 2007). It is known that changes in ENaC activity – when co-expressed in Xenopus oocytes or following dietary Na⁺ restriction in native CD tissue – affects the expression levels of some P2Rs (P2X_{1, 2, 4, 5 and 6} subunits and P2Y₄) (Wildman et al. 2005; 2007). We have proposed that P2Rs may locally regulate ENaC activity in the CD and that some P2Rs could be involved in the pathogenesis of hypertension. To examine the relationship between P2Rs and ENaC in the CD we have investigated P2R mRNA levels in CDs from adult Sprague-Dawley rats maintained on ‘low’ (0.01%), ‘normal’ (0.5%) or ‘high’ (4%) Na⁺ diets (10 days) to alter ENaC expression and activity, and in DOCA-salt hypertensive rats (unilateral nephrectomy and DOCA treatment for 5 weeks; SBP = 189±12 mmHg^-1, n = 6). Kidneys from terminally anaesthetized rats were microdissected and CDs isolated (~15 mm; n = 6 for each sample). RNA was extracted and reverse transcribed, and the cDNA transcripts used for real time-PCR. A ratio was calculated of the P2R gene of interest (either P2X_1-7 or P2Y_{1, 2, 4 and 6}) to a constitutively expressed house-keeping gene (HPRT). We could not detect significant levels (i.e. >0.5 arbitary units; AU) of P2X_{2, 3, 5, 7} and P2Y₁ mRNA under any experimental condition (n = 6). In contrast, significant amounts of mRNA (1-2 AU) were detected for P2X₄ and P2Y_{2 and 6} in CDs from rats on a ‘normal’ Na⁺ intake. CDs from rats on a ‘low’ Na⁺ diet showed a significant increase in abundance of P2X₄ and P2Y₆ mRNA (by 2-fold; n = 6, P < 0.01); CDs from rats maintained on a ‘high’ Na⁺ diet showed a significant decrease in abundance of P2Y₂ mRNA (to less than 0.5 AU; n = 6); CD P2X_{1 and 6} and P2Y₄ mRNA levels were not significant on a ‘normal’ Na⁺ diet, but were increased on a ‘low’ Na⁺ diet (n = 6). However, there were no differences in mRNA expression between ‘normal’ Na⁺ diet and hypertensive rats (n = 6). Thus, P2R mRNA expression levels change in the rat CD in response to changes in dietary Na⁺, but not in DOCA-salt hypertensive rats. From these data it is unlikely that altered CD P2R function plays a role in this model of hypertension.