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

• Published in: Journal of human hypertension Vol. 29; no. 12; pp. 737 - 743
• Main Authors: Williamson, P M, Ong, S L H, Whitworth, J A, Kelly, J J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2015
• Subjects: Adult; Anti-Inflammatory Agents - adverse effects; Aorta; Blood pressure; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Body Weight - drug effects; Comparative analysis; Controlled release; Corticosteroids; Cross-Over Studies; Delayed-Action Preparations; Dosage and administration; Double-Blind Method; Drug therapy; Glucocorticoids; Healthy Volunteers; Hormones; Humans; Hydrocortisone - adverse effects; Hypertension; Hypertension - blood; Hypertension - chemically induced; Hypertension - drug therapy; Isosorbide dinitrate; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - pharmacology; Isosorbide Dinitrate - therapeutic use; Male; Mercury; Nitrates - blood; Nitric oxide; Nitric Oxide Donors - pharmacology; Nitric Oxide Donors - therapeutic use; Nitrites - blood; Patient outcomes; Risk factors; Young Adult; Australia
• ISSN: 0950-9240; 1476-5527
• DOI: 10.1038/jhh.2015.14

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.