Noninvasive assessment of regional arteriolar and arterial dilating properties of lisinopril in healthy volunteers.
The effects of single oral doses of lisinopril (5 and 20 mg) on systemic and regional hemodynamics were investigated noninvasively in a placebo-controlled, randomized, double-blind, cross-over study of 6 healthy male volunteers. Lisinopril induced a dose-dependent (significant after 20 mg) and long-lasting (< or = 8 h) decrease in mean arterial pressure (MAP, approximately 11% after 20 mg) that was related to a decrease in total peripheral resistance (TPR), because simultaneously heart rate (HR) and cardiac output (CO) were unchanged. Brachial artery flow (+42 and +47% after 5 and 20 mg, respectively) and diameter (+8 and +9%) increased significantly, whereas brachial vascular resistance (-31 and -38%) decreased significantly from 2 to 8 h after drug intake. Common carotid artery flow (+20 and +24%) also increased significantly, whereas corresponding resistance (-18 and -26%) decreased significantly during the same period. Finally, CO was significantly redistributed toward the brachial and, to a lesser extent, the carotid vascular beds after both doses of lisinopril. We conclude that in healthy subjects lisinopril, at non- or slightly hypotensive doses, dilates both arterioles and large arteries and that this vasodilation is not homogeneous, affecting preferentially the brachial rather than the carotid vascular bed.
Bellissant
E
E
Service de Pharmacologie Clinique, Hôpital de Bicĕtre, Le Kremlin, France.
Thuillez
C
C
Richer
C
C
Pussard
E
E
Giudicelli
J F
JF
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D017706:Lisinopril / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D017706:Lisinopril