The role of sustained release isosorbide mononitrate on corticosteroid-induced hypertension in healthy human subjects

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.