title: Celecoxib does not alter cardiovascular and renal function during dietary salt loading.
abstract: 1. Cyclo-oxygenase-2 (COX-2)-derived prostaglandins are important in controlling sodium excretion and renin release. In the present study, we tested the hypothesis that a clinical dose of celecoxib would impair urinary sodium excretion and elevate blood pressure (BP) during dietary salt loading. 2. Twelve normotensive individuals (mean (± SEM) age 35 ± 2 years) completed two separate 17 day dietary perturbations, one taking 200 mg/day celecoxib (CX2) and the other taking placebo (PL), randomized with a 1 month wash out. The controlled 17 day diet consisted of a 3 day run-in diet, 7 days of a low-salt (LS, 20 mmol sodium/day) diet and 7 days of a high-salt diet (HS, 350 mmol sodium/day) diet. The order in which the diets were applied was randomized. Data were collected on the last day of the LS and HS diets. 3. Plasma and urinary prostaglandins were modestly lower during celecoxib (P < 0.05). Urinary sodium excretion was greater (P < 0.01) during the HS diet (253 ± 10 vs 281 ± 27 mmol/24 h for PL vs CX2, respectively) compared with the LS diet (14 ± 3 vs 17 ± 7 mmol/24 h for PL vs CX2, respectively; P(drug) = 0.26). Celecoxib did not alter creatinine clearance (P > 0.50). Twenty-four hour mean arterial BP was similar during PL (87 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively) and CX2 (88 ± 2 vs 87 ± 2 mmHg for LS and HS, respectively; P = 0.85), with no effect of dietary salt (P > 0.80). Plasma renin activity, angiotensin II and aldosterone were all suppressed with dietary salt loading (P < 0.05), with no effect of drug (P > 0.35). 4. In conclusion, blood pressure and renal function were not adversely affected by celecoxib, even during dietary salt loading. These findings support current guidelines suggesting minimal cardiovascular risks associated with short-term, low-dose use of celecoxib in young to middle-aged adults.
authors.affiliation: Department of Kinesiology and Applied Physiology, University of Delaware, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Wenner
authors.forename: David G
authors.initials: DG
authors.lastname: Edwards
authors.forename: Chester A
authors.initials: CA
authors.lastname: Ray
authors.forename: William C
authors.initials: WC
authors.lastname: Rose
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Gardner
authors.forename: Michael
authors.initials: M
authors.lastname: Stillabower
authors.forename: William B
authors.initials: WB
authors.lastname: Farquhar
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D010919:Placebos; D011453:Prostaglandins / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology*; D012083:Renin / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010919:Placebos; D011453:Prostaglandins; D011720:Pyrazoles; D017673:Sodium Chloride, Dietary; D013449:Sulfonamides; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D000068579:Celecoxib