RAMIPRIL IN ANGINA-PECTORIS - SHORT-TERM EFFECTS ON GLUCOSE, INSULIN,C-PEPTIDE, ADRENOCORTICOTROPIC HORMONE, AND CORTISOL-LEVELS

We studied the effects of the angiotensin-converting enzyme inhibitor ramipril on plasma levels of adrenocorticotropic hormone (ACTH), corti sol, glucose, insulin, and C-peptide in patients with coronary artery disease. Patients were randomly assigned to treatment with ramipril 5 mg once daily, ramipril 5 mg once daily in combination with 20 mg of t he oral nitrate isosorbide dinitrate (ISDN), ISDN alone 20 mg twice da ily, or placebo. After a 72-hour washout period from their previous va soactive medication, 32 patients (1 woman, 31 men) aged 42 to 72 years (mean age, 63.3 years) received a single dose of the study medication , Plasma levels of ACTH, cortisol, glucose, insulin, and C-peptide wer e measured before drug administration and 1, 2, 3, 4, 5, 6, 8, and 24 hours after drug administration, After the initial 24-hour treatment p eriod, a randomized, double-masked, placebo-controlled, four-way, cros sover phase started in which each patient was treated with each study medication for 1 week, Individual treatment phases were separated by w eekly washout periods, and plasma levels of insulin, C-peptide, and gl ucose were assessed in the morning at trough and 3 hours after intake of the study medication, The typical circadian variation was observed for cortisol, without any difference between the four treatment groups , On average, ACTH levels were significantly higher in the patients tr eated with ISDN alone, No significant effect on glucose, insulin, or C -peptide levels was observed among patients receiving the first dose o f ramipril, ISDN, ramipril + ISDN, or placebo, nor between the crossov er phases during continued treatment, We conclude that in patients wit h angina pectoris, a single dose of ramipril has no acute effects on i nsulin secretion and glucose utilization, nor does multiple dosing of ramipril affect glucose homeostasis. Ramipril also did not affect circ adian cortisol secretion, These findings also pertain to the combinati on of ramipril and ISDN, In contrast, after administration of a single dose of ISDN alone, a statistically significant increase in ACTH leve ls was observed, The increase in ACTH levels could be a marker for sym pathetic nervous system activation resulting from counterregulation.