Inhibitory effect of a novel antianginal agent, E4080, on ST segment elevation induced by vasopressin in anesthetized guinea pigs.
We compared the antianginal effect of E4080, a novel bradycardiac agent with coronary vasodilating properties, with those of a bradycardiac agent and some coronary vasodilators in vasopressin-induced anginal model of guinea pigs. An i.v.-administration of vasopressin (0.2 IU/kg) produced an ST segment elevation on electrocardiograms (ECG) of 0.30 +/- 0.05 mV from the baseline within 30 sec in anesthetized guinea pigs. The ST segment elevation on ECG was used as an index of myocardial ischemia. E4080 and other drugs were injected i.v. 5 min before the administration of vasopressin. E4080 at 5 mg/kg depressed the ST segment elevation induced by vasopressin to 0.06 +/- 0.01 mV (20% of control, n = 6, P < 0.001). However, alinidine (5 mg/kg), which produced the same bradycardic action (reduction of heart rate by 50%) as that of E4080, tended to inhibit the ST segment elevation, but this was not statistically significant. On the other hand, other vasodilators such as isosorbide dinitrate (0.3 mg/kg), nifedipine (0.1 mg/kg) and lemakalim (1 mg/kg) also significantly reduced the ST segment elevation to 0.16 +/- 0.03, 0.08 +/- 0.04 and 0.09 +/- 0.03 mV, respectively. These results suggest that the inhibitory effect of E4080 on the ST segment elevation induced by vasopressin is due to the coronary vasodilating effect rather than the bradycardiac effect, and that E4080 would be useful as an antianginal agent.
Kodama
K
K
Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
Adachi
H
H
Ogawa
T
T
Ohhara
H
H
D000758:Anesthesia; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D019806:Cromakalim; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D001578:Benzopyrans; D002317:Cardiovascular Agents; D002396:Catechols; D007093:Imidazoles; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D014667:Vasopressins; C072129:E 4080; C022192:alinidine; D009543:Nifedipine; D007548:Isosorbide Dinitrate; D003000:Clonidine