Rytz Chantal L, Dumanski Sandra M, Sola Darlene Y, Ahmed Sofia B
Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.
CJC Open. 2022 Nov 17;5(2):112-119. doi: 10.1016/j.cjco.2022.11.011. eCollection 2023 Feb.
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.
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.
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 ( = 0.2) and diastolic (D)BP ( = 0.1) were similar between sexes. Post-COX-2 inhibition, resting SBP ( < 0.001) and DBP ( = 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: = 0.54; change in PWV: = 0.55; females vs males). COX-2 inhibition was associated with increased SBP ( = 0.039 vs pre-COX-2 inhibition), but no change in DBP ( = 0.16) or PWV ( = 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: = 0.88; DBP: = 0.93; PWV: = 0.97).
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.
心血管疾病是全球主要的死亡原因。环氧化酶（COX）衍生的前列腺素在心血管健康调节中起重要作用。动物研究表明，女性受试者的血管对前列腺素的依赖性更强，但这是否适用于人类尚不清楚。我们旨在评估COX-2抑制对成年人类血压和动脉僵硬度（心血管风险的有效标志物）的影响。
在两个相同的研究日，对健康的绝经前女性和男性进行研究，在每日口服200毫克塞来昔布14天前后进行高盐平衡试验。在基线时以及对血管紧张素II（AngII）刺激（肾素-血管紧张素-醛固酮系统活性的有效标志物）的反应中测量血压（BP）和脉搏波速度（PWV）。
研究了13名女性（年龄[平均值±标准差]，38±13岁）和11名男性（年龄，34±9岁）。在COX-2抑制之前，男女之间收缩压（S）BP（P = 0.2）和舒张压（D）BP（P = 0.1）的静息测量值相似。COX-2抑制后，女性的静息SBP（P < 0.001）和DBP（P = 0.02）显著低于男性。COX-2抑制与按性别划分的动脉参数变化无关（DBP变化：P = 0.54；PWV变化：P = 0.55；女性与男性）。COX-2抑制与女性SBP升高（P = 0.039，与COX-2抑制前相比）相关，但对AngII刺激的DBP（P = 0.16）或PWV（P = 0.52）反应无变化。男性在COX-2抑制前后对AngII的反应测量值无差异（SBP：P = 0.88；DBP：P = 0.93；PWV：P = 0.97）。
COX-2抑制对动脉功能的影响可能因性别而异，但需要进一步研究。鉴于非甾体抗炎药（NSAIDs）与心血管风险之间的关联，有必要更多地关注性别特异性病理生理学。
