RESPONSES TO LOW-DOSE INTRAVENOUS PERINDOPRILAT INFUSION IN SALT DEPLETE SALT REPLETE NORMOTENSIVE VOLUNTEERS

1 Intravenous ACE inhibitor therapy appears to have a role in the treatment of acute heart failure and early after myocardial infarction. Practical experience with intravenous administration with activation of renin is limited. We report responses to perindoprilat (Pt, 0.67 mg) or placebo (P) infused over 4 h in normotensive male volunteers (n = 12, 19-28 years, 53-77 kg) with double-blind, placebo controlled salt depletion (SD) or salt repletion (SR) as a model of the activated renin system. 2 Salt depletion caused no significant fall in serum sodium (P, 139.4 +/- 2.4; Pt, 138.3 +/- 1.9) compared with salt replete preparation (P, 139.9 +/- 1.2; Pt, 139,7 +/- 0.9) but elevation of plasma renin activity 2-3-fold. Pretreatment baseline systolic blood pressure following salt depletion (P, 121 +/- 9.3/71 +/- 7.9; Pt, 121.5 +/- 9.6/69 +/- 8.1) was higher than following salt replete preparation (P, 114 +/- 9.5/61 +/- 7.2; Pt, 116.9 +/- 6.9/67 +/- 7.2). 3 Baseline corrected supine SBP fell significantly and to a similar extent following active treatment regardless of activation of the renin system (SD, -14.6 +/- 9.5/-9.4 +/- 6.4; SR, -12 +/- 14/-10.1 +/- 6.6) compared with placebo (SD, -6.1 +/- 6/-3.7 +/- 5.6; SR, -4.7 +/- 10/-1.3 +/- 6.5). Heart rate was unchanged. Blood pressure response peaked at 4 h coincident with the end of infusion, peak drug concentration (SD, 15.8 +/- 2.5 ng ml(-1); SR, 16 +/- 2.8 ng ml(-1)) and mean maximal plasma ACE inhibition (SD, 2.7 +/- 0.9 EU 1(-1) SR, 2.7 +/- 0.7 EU 1(-1); compared with P; SD, 25.5 +/- 6 EU 1(-1); SR, 24.7 +/- 5.6 EU 1(-1)). BP recovered rapidly following discontinuation of infusion. 4 Controlled onset of ACE inhibition is feasible following low dose constant rate infusion of perindoprilat. Modest and predictable falls in blood pressure occur. This may have clinical application in heart failure where blood pressure control is important. The blood pressure response to low doses of ACEI, as used to initiate therapy in heart failure, may not depend solely on AngII withdrawal as activation of the RAS appears not to affect the response.