Williamson P M, Ong S L H, Whitworth J A, Kelly J J
Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Department of Renal Medicine, St George Hospital, Kogarah, New South Wales, Australia.
J Hum Hypertens. 2015 Dec;29(12):737-43. doi: 10.1038/jhh.2015.14. Epub 2015 Mar 26.
There is evidence implicating abnormalities in the nitric oxide (NO) pathway in the development of glucocorticoid-induced hypertension (GC-HT). In humans, a reduction in NO availability during cortisol treatment has been observed. This study examined whether the NO donation may reverse the elevated blood pressure (BP) observed with cortisol treatment. A randomised double-blind, placebo-controlled, crossover study was undertaken in eight healthy men to address the effect of co-administration of isosorbide mononitrate (ISMN, 60 mg single dose, day 5) with cortisol (200 mg per day, days 1-6) and then compared with placebo (single dose, day 5) with cortisol. After a 2-week washout period, subjects crossed over to the alternate treatment. BP measurements were obtained using a mercury sphygmomanometer. Tonometry was used to estimate central pressures. There was a significant rise in mean arterial pressure with cortisol: 80 ± 3 vs 89 ± 3 mm Hg (day 1 vs day 5, cortisol+ISMN phase, P < 0.001) and 81 ± 3 vs 89 ± 3 mm Hg (day 1 vs day 5, cortisol+placebo phase, P < 0.01). ISMN significantly decreased aortic augmentation index: -17.3 ± 3.2 vs 1.8 ± 3.5%, (differences calculated from day 5-day 1, cortisol/ISMN vs cortisol+placebo, P < 0.001). These results demonstrated that GC-HT can be modified by co-administration of exogenous NO donors, consistent with the hypothesis that GC-HT is accompanied by reduced NO activity in humans.
有证据表明，一氧化氮（NO）途径异常与糖皮质激素诱导的高血压（GC-HT）的发生有关。在人类中，已观察到皮质醇治疗期间NO可用性降低。本研究探讨了给予NO是否可以逆转皮质醇治疗所观察到的血压升高。对8名健康男性进行了一项随机双盲、安慰剂对照的交叉研究，以探讨单硝酸异山梨酯（ISMN，60 mg单剂量，第5天）与皮质醇（每天200 mg，第1 - 6天）联合给药的效果，然后与皮质醇加安慰剂（单剂量，第5天）进行比较。经过2周的洗脱期后，受试者交叉接受替代治疗。使用汞柱血压计测量血压。采用眼压测量法估计中心血压。皮质醇治疗后平均动脉压显著升高：80±3 vs 89±3 mmHg（第1天 vs 第5天，皮质醇+ISMN阶段，P<0.001）以及81±3 vs 89±3 mmHg（第1天 vs 第5天，皮质醇+安慰剂阶段，P<0.01）。ISMN显著降低了主动脉增强指数：-17.3±3.2 vs 1.8±3.5%（第5天 - 第1天计算的差值，皮质醇/ISMN vs 皮质醇+安慰剂，P<0.001）。这些结果表明，联合给予外源性NO供体可以改善GC-HT，这与GC-HT在人类中伴有NO活性降低的假设一致。
