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Effect of COX‐2 inhibition on sodium excretion and ENaC expression in Angiotensin II induced hypertensive rats
Author(s) -
Gonzalez Alexis A,
Cespedes Carlos,
Villanueva Sandra,
Vio Carlos P
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.605.12
Subject(s) - epithelial sodium channel , endocrinology , medicine , excretion , angiotensin ii , renin–angiotensin system , chemistry , celecoxib , renal medulla , cyclooxygenase , kidney , prostaglandin e2 , prostaglandin , prostaglandin e , sodium , enzyme , blood pressure , biochemistry , organic chemistry
Experimental evidence demonstrates that Prostaglandin E2 (PGE2) production promotes salt excretion in the renal medulla in a setting of activation of the renin‐angiotensin‐system (RAS). We hypothesized that cyclooxygenase‐2 (COX‐2) inhibition in Angiotensin II (Ang II)‐induced hypertensive rats causes Na+ retention by altering the expression of the Epithelial Sodium Channel (ENaC). Sham‐operated male Sprague‐Dawley rats (n=8) were compared to Ang II infused rats (0.4μg/kg/min, n=6) and Ang II infused + COX‐2 inhibitor; Celecoxib (30 mg/kg/d, n=6). After 5 days, Na+ excretion was increased in Ang II (1.37 ± 0.19 vs. 0.74 ± 0.03 mEq/day; P<0.05) and Ang II + Celecoxib (1.34 ± 0.14 vs. 0.74 ± 0.03 mEq/day; P<0.05) groups. PGE2 urinary excretion was augmented in Ang II infused rats (1,261 ± 147 vs. 643 ± 31 pg/h; P<0.05), while Celecoxib suppressed this effect (596 ± 39 vs. 643 ± 31 pg/h; P=NS). COX‐2 protein abundance was increased in the renal medulla of Ang II and Ang II + Celecoxib groups. The mRNA and protein levels of αENaC subunit were up‐regulated in cortex and medulla. No difference in αENaC expression was found between Ang II and Ang II plus Celecoxib groups. These results demonstrate the induction of αENaC expression in Ang II‐induced hypertensive rats and suggest that the up‐regulation of medullary COX‐2 is not involved in ENaC regulation and Na+ handling during chronic RAS activation.