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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.
AuthorsP M Williamson, S L H Ong, J A Whitworth, J J Kelly
JournalJournal of human hypertension (J Hum Hypertens) Vol. 29 Issue 12 Pg. 737-43 (Dec 2015) ISSN: 1476-5527 [Electronic] England
PMID25810066 (Publication Type: Journal Article, Randomized Controlled Trial)
Chemical References
  • Anti-Inflammatory Agents
  • Delayed-Action Preparations
  • Nitrates
  • Nitric Oxide Donors
  • Nitrites
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate
  • Hydrocortisone
Topics
  • Adult
  • Anti-Inflammatory Agents (adverse effects)
  • Blood Pressure (drug effects)
  • Blood Pressure Monitoring, Ambulatory
  • Body Weight (drug effects)
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Hydrocortisone (adverse effects)
  • Hypertension (blood, chemically induced, drug therapy)
  • Isosorbide Dinitrate (analogs & derivatives, pharmacology, therapeutic use)
  • Male
  • Nitrates (blood)
  • Nitric Oxide Donors (pharmacology, therapeutic use)
  • Nitrites (blood)
  • Young Adult

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