The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo.
1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.
Prostran
M
M
Department of Pharmacology, Faculty of Medicine, Belgrade, Yugoslavia.
Samardzić
R
R
Todorović
Z
Z
Jovanović-Mićić
D
D
Japundzić
N
N
Beleslin
B D
BD
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D004656:Enalapril; D002216:Captopril; D001920:Bradykinin