Abstract
BACKGROUND: Cardiovascular disease is the leading cause of death globally. Cyclooxygenase (COX)-derived prostaglandins play an important role in cardiovascular health regulation. Animal studies suggest a greater vascular dependence on prostaglandins in female subjects, but whether this extends to humans is unknown. We aimed to assess the effect of COX-2 inhibition on blood pressure and arterial stiffness, validated markers of cardiovascular risk, in human adults. METHODS: Healthy premenopausal females and males were studied in high-salt balance before and after 14 days of daily oral celecoxib, 200 mg ingestion, on 2 identical study days. Blood pressure (BP) and pulse-wave velocity (PWV) were measured at baseline and in response to an Angiotensin II (AngII) challenge, a validated marker of renin-angiotensin-aldosterone system activity. RESULTS: Thirteen females (age [mean ± standard deviation], 38 ± 13 years) and 11 males (age, 34 ± 9 years) were studied. Pre-COX-2 inhibition, resting measures of systolic (S)BP (P = 0.2) and diastolic (D)BP (P = 0.1) were similar between sexes. Post-COX-2 inhibition, resting SBP (P < 0.001) and DBP (P = 0.02) were significantly lower in females than in males. COX-2 inhibition was not associated with changes in arterial parameters by sex (change in DBP: P = 0.54; change in PWV: P = 0.55; females vs males). COX-2 inhibition was associated with increased SBP (P = 0.039 vs pre-COX-2 inhibition), but no change in DBP (P = 0.16) or PWV (P = 0.52) response to AngII challenge in females. Measures did not differ in response to AngII pre- vs post-COX-2 inhibition in males (SBP: P = 0.88; DBP: P = 0.93; PWV: P = 0.97). CONCLUSIONS: The effects of COX-2 inhibition on arterial function may differ by sex, but further studies are needed. Given the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, increased attention regarding sex-specific pathophysiology is warranted.