Improvement of bradykinin endothelium-mediated vasodilation of forearm resistance circulation by quinaprilat in patients with coronary artery disease with or without left ventricular dysfunction.
Angiotensin-converting enzyme (ACE) inhibition potentiates bradykinin and acetylcholine endothelium-mediated vasodilation. Three groups were studied. Group I (n = 10) was the reference group; group II was composed of nine patients with coronary artery disease; and group III of seven patients with coronary artery disease and left ventricular dysfunction. Forearm blood flow was measured with plethysmography. Acetylcholine and bradykinin were administered in a random order in the brachial artery at infusion rates of 40 and 80 microg/min and 10, 30, 100 pmol/min, respectively. Then quinaprilat was infused alone at the rate of 50 microg/min and then coinfused with acetylcholine and bradykinin. Five of the reference subjects were pretreated with acetylsalicylate. Acetylcholine and bradykinin increased forearm blood flow in a dose-dependent manner in the three groups. However, the vasodilator responses to both agents were significantly lower in the two groups of patients than in the reference group. Quinaprilat significantly enhanced the vasodilator response to acetylcholine only in subjects of the reference group, whereas it enhanced the vasodilator response to each dose of bradykinin, both in subjects of the reference group and in patients. Pretreatment with aspirin did not change the vasodilator responses in any group. In healthy persons, quinaprilat had no effect on its own on forearm blood flow but enhanced the response to bradykinin and even acetylcholine. In patients with coronary disease, short-term administration of quinaprilat was able to improve the impaired response to bradykinin. The response to acetylcholine, however, could not be significantly enhanced in contrast to that in healthy subjects.
Benacerraf
S
S
Service des Explorations Fonctionnelles, Fédération de Cardiologie et Institut National de la Santé et de la Recherche Médicale, U400, Créteil, France.
Carville
C
C
Adnot
S
S
Montagne
O
O
Sediame
S
S
Belhassen
L
L
Dubois-Randé
J L
JL
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000188:drug therapy
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D010975:Platelet Aggregation Inhibitors; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D012083:Renin; D000109:Acetylcholine; D001241:Aspirin; D001920:Bradykinin