ESPN 51th Annual Meeting

ESPN 2018

The effect of cyclooxigenase-2 inhibition on skin sodium- and water content of sodium-overloaded rats
Róbert Agócs 1 Dániel Sugár 1 Domonkos Pap 2 Endre Sulyok 3 Attila J. Szabó 2 Tivadar Tulassay 2

1- 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary
2- MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
3- Faculty of Health Sciences, University of Pécs, Pécs, Hungary

Dietary salt overload increases the amount of sodium-binding glycosaminoglycans (GAGs) as well as VEGF-C induced lymphangiogenesis in the skin. Selective cyclooxygenase-2 (COX2) inhibitors interfere with lymph vessel formation by blocking COX2-VEGFC pathway. COX2 inhibition results in sodium retention and hypertension, and salt overload generates high blood pressure too. We investigated the influence of the oral COX2 inhibitor celecoxib on blood pressure (BP), sodium handling and sodium- and water content of the skin (SNa and SW) in sodium-overloaded rats.


Material and methods:

Twenty-four, 8-week old, male Wistar rats in 3 groups received the following diet/medication for two weeks: low-salt diet (NaCl<0.01% m/m) + vehicle (LSD+V); high-salt diet (NaCl=8% m/m) + vehicle (HSD+V); high-salt diet + celecoxib (20mg/kg/day)(HSD+C). BP, urine sodium concentration (UNa), as well as SNa and SW was determined.


UNa increased in HSD+V group compared to that of LSD+V animals. COX2 inhibition attenuated UNa in HSD+C rats (LSD: 14+-8mmol/l, HSD+V: 154+-66mmol/l, HSD+C: 82+-34mmol/l; LSD+V vs HSD+V p<0,001, HSD+V vs HSD+C p<0,05, LSD+V vs HSD+C p<0,05). Systolic- and diastolic BP of HSD+C animals increased (137+-7 vs 118+-12mmHg for systolic, and 95+-7 vs 80+-9mmHg for diastolic, p<0,01 vs LSD+V). BP of HSD+V group did not differ from that of LSD+V. SNa in sodium-overloaded groups were higher than in the LSD+V group (LSD+V: 3,9+-0,4mg/g dry skin, HSD+V: 6,2+-0,5mg/g, HSD+C: 6,6+-1,2mg/g; LSD+V vs HSD+V/HSD+C p<0,01). No difference appeared between HSD+V and HSD+C groups. SW exhibited similar differences.



Sodium overload in combination with COX2 inhibition resulted in high BP. Elevated UNa was partly reduced by COX2 inhibition. In spite of the increased sodium-retention in HSD+C group, sodium- and water content of the skin did not differ from that of HSD+V group. We hypothesize that the saturation of the sodium-binding capacity of the skin (GAG formation) exhausted due to the blockade of COX2 pathway in sodium overload.

Supported by the ÚNKP-17-3-III-SE-31 grant of the Ministry of Human Capacities and the OTKA grant K125470.