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

Abstract

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. Show more