The anti-tachycardic mechanism of a direct-acting vasodilator, budralazine, in rats.
The present study was undertaken to elucidate the anti-tachycardic effect of a direct-acting vasodilator, budralazine, using an electrophysiological technique. Normotensive male Wistar rats were used. Rats were anesthetized intraperitoneally with urethane and alpha-chloralose. Intravenous administration of budralazine (0.5-5.0 mg/kg) produced a dose-dependent reduction of mean arterial pressure in anesthetized rats. At doses of 0.5 and 1.0 mg/kg, budralazine induced bradycardia accompanied with a decrease in cardiac sympathetic nerve activity (ICNA). Preganglionic adrenal sympathetic nerve activity (ASNA) was also reduced by budralazine (1.0 mg/kg). A 0.5 mg/kg of budralazine neither influenced carotid sinus nerve activity nor augmented aortic depressor nerve activity (ADNA). On the contrary, at dose of 5.0 mg/kg, budralazine produced a tachycardia accompanied with increases in both ICNA and ASNA. The ADNA was decreased by budralazine (5.0 mg/kg) significantly. These findings suggest that the central sympathoinhibitory action of budralazine may be responsible for the anti-tachycardic effect of budralazine and baroreceptor-mediated tachycardia occurred after high dose of budralazine.
Yoshioka
M
M
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Minami
M
M
Saito
H
H
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002346:Carotid Sinus / Q000294:innervation; D004525:Efferent Pathways / Q000187:drug effects; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D006830:Hydralazine; C006153:budralazine