The Role of Imdur in Cortisol-Induced Hypertension in Humans

INTERVENTION: Healthy human subjects will be treated with oral hydrocortisone 200mg per day for 5 days. Blood pressure and metabolic parameters will be measured regularly. On the last day of hydrocortisone treatment, a single dose of oral isosorbide mononitrate will be given and the effect of this dose on blood pressure will be measured.Hydrocortisone will be administered at a dose of 50mg four times per day to provide a total daily dose of 200mg hydrocortisone per day. Isosorbide mononitrate will be administered as a single oral dose of 60mg. It will be administered on the morning to the 5th hydrocortisone treatment day prior to the 17th dose of oral hydrocortisone (out of a total of 20 doses of hydrocortisone administered over the whole treatment phase). Oral hydrocortisone administration at a dose of 200mg per day is expected to result in a number of metabolic changes including weight gain, elevation of white cell count, plasma glucose and cortisol concentrations, and reductions in plasma potassium and haematocrit. Compliance with therapy will be assessed by a pill count on each attendance at the clinical study centre, Additionally at the beginning and end of each treatment phase measurement of body weight, plasma electrolytes, glucose and cortisol concentrations and measurement of haematocrit and white cell count will be undertaken, There will be a minimum two week wash out period between each treatment phase. CONDITION: Hypertension PRIMARY OUTCOME: Central pressure measurements will be assessed non‐invasively by applanation tonometery of the radial artery. The primary outcome is the change in blood pressure on the last day of hydrocortisone treatment after isosorbide mononitrate (or placebo) is co‐administered. Blood pressure is measured by standard cuff measurement, and ambulatory blood pressure monitoring. SECONDARY OUTCOME: Plasma nitrate / nitrite activity INCLUSION CRITERIA: Healthy male volunteers on no regular medications