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.

High dietary sodium intake impairs endothelium-dependent dilation in healthy salt-resistant humans

“…This was followed by 7 days of a low sodium (LS) diet (20 mmol sodium/day) and 7 days of a high sodium (HS) diet (300-350 mmol sodium/day), in random order. The specific sodium intakes were chosen in order to accurately classify adults with salt-resistant BP and are in agreement with previously published studies [23-25]. Dietary potassium intake averaged 70.9 ± 3.7 mmol/day, and the percentage of carbohydrates were 50%, fat 30%, and protein 20% across all conditions.…”

Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress

“…After completing the run-in diet, subjects were assigned to 7 days of a low-sodium diet (LS; 20 mmol day −1 ) and 7 days of a high-sodium diet (HS; 300-350 mmol day −1 ), in a randomized order. These target sodium intakes were selected to allow us to appropriately classify adults with salt-resistant BP and are consistent with previously published studies (He et al 2001;Eisenach et al 2011;Wenner et al 2011). Food items provided constant daily amounts of carbohydrates (50%), fat (30%) and protein (20%).…”

Regulation and function of renal medullary cyclooxygenase-2 during high salt loading

“…NSAIDs are among the most widely prescribed drugs worldwide and are associated with sodium retention and hypertension, particularly in patients with preexisting hypertension (49), (50), (51). Although it is recently reported that celecoxib did not alter cardiovasucular and renal function during dietary salt loading with short-term, low-dose use of celecoxib in young to middle-aged adults,(52) most of clinical and animals’ studies still support the theory that COX-2-derived prostanoids resist the development of fluid retention and hypertension (53). More than 50 clinical trials involving 13,000 subjects have shown that edema is among the most common side effects of COX-2 inhibition (54).…”