title: 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.
authors: Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors: P M
authors: PM
authors: Williamson
authors: 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.
authors: S L H
authors: SL
authors: Ong
authors: John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
authors: J A
authors: JA
authors: Whitworth
authors: 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.
authors: J J
authors: JJ
authors: Kelly
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D001835:Body Weight / Q000187:drug effects; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects*; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009566:Nitrates / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D009573:Nitrites / Q000097:blood; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D006854:Hydrocortisone