Cyclooxygenase inhibition and baroreflex sensitivity in humans.
Cyclooxygenase inhibition and baroreflex sensitivity in humans.
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人类环加氧酶抑制和压力反射敏感性。
DOI：
10.1152/ajpheart.00357.2004
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Ray,ChesterA
中科院分区：
文献类型：
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作者：
Monahan,KevinD;Ray,ChesterA
动物研究表明，类前列腺素（如前列环素）可能使压力感受器和/或压力反射反应敏感或受损，这取决于给药部位和/或抑制作用。我们验证了一个假设，即急性抑制环氧化酶（COX）（前列腺素合成中的限速酶）会损害人类心脏周期（R-R间期）和肌肉交感神经活动（MSNA）的压力反射调节，并增强加压反应性。在基线（输注前）和（输注后）静脉输注COX拮抗剂（酮洛酸，45 mg）（24±1年，n= 12）或生理盐水（25±1年，n= 12）后60分钟测定气压反射敏感性（BRS）。BRS采用改良的Oxford技术（静脉滴注硝普赛，随后滴注苯肾上腺素）进行评估。BRS被量化为1)R-R间期-收缩压关系（心血管BRS）和2)msna -舒张压关系（交感神经BRS）在动脉血压药理变化过程中的线性部分的斜率。Ketorolac没有改变心血管（输注前和输注后分别为19.4±2.1 vs 18.4±2.4 ms/mmHg）或交感神经BRS(- 2.9±0.7 vs - 2.6±0.4任意单位·beat - 1·mmHg - 1)，但显著降低前列腺素生成的血浆生物标志物（血浆血栓素B2） 53±11%。对照（生理盐水输注）组心血管BRS（21.3±3.8 vs 21.2±3.0 ms/mmHg）、交感BRS（- 3.4±0.3 vs - 3.2±0.2任意单位·beat - 1·mmHg - 1）、血栓素B2（- 1±12%）变化不变。酮洛酸对稳定状态（0.5、1.0和1.5 μg·kg−1·min−1）输注（5 min/剂量）的苯肾上腺素的升压反应没有改变（n= 8）。总的来说，这些数据表明，COX酶的急性药理拮抗作用不会损害健康年轻人的BRS（心血管或交感神经）或增强升压反应性。
Animal studies suggest that prostanoids (i.e., such as prostacyclin) may sensitize or impair baroreceptor and/or baroreflex responsiveness depending on the site of administration and/or inhibition. We tested the hypothesis that acute inhibition of cyclooxygenase (COX), the rate-limiting enzyme in prostanoid synthesis, impairs baroreflex regulation of cardiac period (R-R interval) and muscle sympathetic nerve activity (MSNA) in humans and augments pressor reactivity. Baroreflex sensitivity (BRS) was determined at baseline (preinfusion) and 60 min after (postinfusion) intravenous infusion of a COX antagonist (ketorolac; 45 mg) (24 ± 1 yr;n= 12) or saline (25 ± 1 yr;n= 12). BRS was assessed by using the modified Oxford technique (bolus intravenous infusion of nitroprusside followed by phenylephrine). BRS was quantified as the slope of the linear portion of the1) R-R interval-systolic blood pressure relation (cardiovagal BRS) and2) MSNA-diastolic blood pressure relation (sympathetic BRS) during pharmacological changes in arterial blood pressure. Ketorolac did not alter cardiovagal (19.4 ± 2.1 vs. 18.4 ± 2.4 ms/mmHg preinfusion and postinfusion, respectively) or sympathetic BRS (−2.9 ± 0.7 vs. −2.6 ± 0.4 arbitrary units·beat−1·mmHg−1) but significantly decreased a plasma biomarker of prostanoid generation (plasma thromboxane B2) by 53 ± 11%. Cardiovagal BRS (21.3 ± 3.8 vs. 21.2 ± 3.0 ms/mmHg), sympathetic BRS (−3.4 ± 0.3 vs. −3.2 ± 0.2 arbitrary units·beat−1·mmHg−1), and thromboxane B2(change in −1 ± 12%) were unchanged in the control (saline infusion) group. Pressor responses to steady-state incremental (0.5, 1.0, and 1.5 μg·kg−1·min−1) infusion (5 min/dose) of phenylephrine were not altered by ketorolac (n= 8). Collectively, these data indicate that acute pharmacological antagonism of the COX enzyme does not impair BRS (cardiovagal or sympathetic) or augment pressor reactivity in healthy young adults.