The assessment of ACE activity in man following angiotensin I challenges: a comparison of cilazapril, captopril and enalapril.
1. The aim of the studies was to develop a new methodology to estimate the pharmacodynamic properties and potency of angiotensin converting enzyme (ACE) inhibitors in man. 2. Angiotensin I dose-response curves were derived by continuous infusion of angiotensin I in increasing dose steps; steady state was reached within 3 min. 3. Interaction between angiotensin I (agonist) and ACE inhibitors (antagonist) was characterized according to Schild-plot methodology by measuring agonist dose-response curves using diastolic blood pressure in the absence and the presence of varying doses of the antagonist. 4. Cilazapril shifted the angiotensin I dose-response curves to the right. A twofold shift (apparent Ki-dose) was observed with approximately 0.6 mg cilazapril. 5. The effect of angiotensin I on diastolic blood pressure was determined before and up to 36 h after administration of 25 mg captopril, 10 mg enalapril, 4 mg cilazapril and a placebo orally. The pharmacodynamic half-life of captopril was about 2 h, whereas the effect of enalapril and cilazapril was about 4 h. 6. Angiotensin I dose-response curves are useful methods of investigating the pharmacodynamic properties of ACE-inhibitors in man.
Essig
J
J
Zentrum für Kardiovaskuläre Pharmakologie, ZeKaPha GmbH, Wiesbaden, Federal Republic of Germany.
Belz
G G
GG
Wellstein
A
A
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D017315:Cilazapril; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011724:Pyridazines / Q000494:pharmacology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D000804:Angiotensin II; D017315:Cilazapril; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A