Systemic and regional hemodynamic effects of zabicipril in healthy volunteers.
The effects of two oral doses of zabicipril, a new angiotensin converting enzyme inhibitor, on systemic (arterial pressure, heart rate, and cardiac output) hemodynamic parameters and regional (brachial, carotid and femoral arteries' diameters and flows) hemodynamic parameters and on biologic (plasma-converting enzyme and renin activities, catecholamines, and atrial natriuretic factor) parameters were noninvasively investigated and compared with those of a placebo in a double-blind crossover study performed in six healthy male volunteers. Although it did not affect the systemic hemodynamic parameters, zabicipril induced a strong peripheral vasodilation, significantly reducing brachial, carotid, and femoral resistances and increasing the corresponding blood flows from 3 or 4 1/2 hours to 9 hours. This vasodilation affected only the arterioles, not the large arteries, and resulted in a redistribution of cardiac output toward the three regional vascular beds. Zabicipril induced an early, potent, and long-lasting converting enzyme inhibition. Furthermore, zabicipril did not affect plasma catecholamines and atrial natriuretic factor.
Bellissant
E
E
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Thuillez
C
C
Pussard
E
E
Giudicelli
J F
JF
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004311:Double-Blind Method; D004341:Drug Evaluation; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002395:Catecholamines; C065499:zabicipril; D009320:Atrial Natriuretic Factor