Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA251

Poster Communications

The importance of Cox-2 in interstitial cells of the renal medulla for kidney function and salt handling

M. Fuchs1, K. Gerl1, J. Schrankl1, A. Kurtz1

1. Physiology, University of Regensburg, Regensburg, Bavaria, Germany.


Within the kidney cyclooxygenase-2 (Cox-2) is found in the macula densa cells of the cortical distal tubule and in nondefined interstitial cells of the inner medulla. Cox-2 expression at these sites is oppositely regulated by the dietary salt intake. Whilst a mediator role of Cox-2 in macula densa cells for the regulation of renin synthesis and secretion is meanwhile well accepted, the functional relevance of Cox-2 in medullary cells is not that clear. A role of medullary Cox-2 derived prostaglandins for salt dependent blood pressure regulation has been discussed in this context. It was the aim of this study to characterize medullary Cox-2 expressing cells by identifying distinct cellular markers, using the co-in-situ hybridization RNAscope® technique and to investigate the functional role of their Cox-2 expression under a normal and increased salt intake in mice. To evaluate the functional relevance of Cox-2 we assessed basic key parameters of renal function, such as blood pressure, glomerular filtration rate (GFR), urine osmolality and renal electrolyte excretion in mice deficient of Cox-2 in medullary cells. Results are given as means ± S.E.M. Utilizing co-in-situ hybridization, we could identify PDGFR-β and Tenascin-C as markers for Cox-2 expressing medullary interstitial cells, whilst, there was only a marginal co-expression of Cox-2 with other renal interstitial markers, such as CD73 and NG2. For investigating the functional relevance of Cox-2 in interstitial cells of the renal medulla, we generated mice with a tamoxifen inducible deletion of Cox-2 under control of the PDGFR-β promoter. After functional assessment under normal salt intake, the mice were fed a high salt diet containing 4% sodium chloride. With a normal salt intake, the above-mentioned kidney functions remained unchanged after the deletion of Cox-2. In the control animals we could observe a marked increase in the number of Cox-2 expressing cells under a higher salt intake. Furthermore to compensate a higher dietary salt intake the GFR rose in control animals (950,4±29,2 to 1350±69,2 µl/100g BW, n=9) in line with an increased sodium excretion, while the blood pressure of these animals remained unchanged. In Cox-2 deficient mice, the rise in GFR was attenuated (890,1±28,8 to 1171±40,4 µl/100g BW, n=15) and the compensatory increase of urine osmolality as seen in control animals was reduced (1629±40,2 for controls vs. 1363±82 mOsmol/L, n=11). In addition the Cox-2 deficient animals showed a significant rise in blood pressure (119,2±1,4 for controls vs. 140,6±2 mmHg, n=3). Our results indicate that renal medullary Cox-2 expressing cells belong to the pool of PDGFR-β+ interstitial cells, that also express Tenascin-C. Furthermore, our findings suggest that Cox-2 in medullary cells significantly contributes to salt and blood pressure homeostasis.

Where applicable, experiments conform with Society ethical requirements