[Anti-tachycardiac effect of a direct-acting vasodilator, budralazine].
The present study was undertaken to elucidate the anti-tachycardiac 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. After immobilization with gallamine triethiodide, respiration was maintained through a tracheal cannula connected rodent respirator. Intravenous administration of budralazine (0.5, 1.0 and 5.0 mg/kg) produced a dose-dependent reduction of mean arterial pressure. At doses of 0.5 and 1.0 mg/kg, budralazine induced bradycardia accompanied with a decrease in cardiac sympathetic nerve activity. Plasma norepinephrine concentration was reduced by budralazine (0.5 mg/kg). Preganglionic adrenal sympathetic nerve activity 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. On the contrary, at dose of 5.0 mg/kg, budralazine produced a tachycardia accompanied with increases in both cardiac sympathetic nerve activity. In addition, plasma epinephrine concentration was also increased at a dose of 5.0 mg/kg. The aortic depressor nerve activity was decreased by budralazine (5.0 mg/kg) significantly. When equi-hypotensive doses of budralazine and clonidine were compared, the renal sympathoinhibitory potency of budralazine was less than that of clonidine. These findings suggest that the central sympathoinhibitory action of budralazine may be responsible for the anti-tachycardiac effect of budralazine.
Yoshioka
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000494:pharmacology*; D014665:Vasodilator Agents
D002395:Catecholamines; D013565:Sympatholytics; D014665:Vasodilator Agents; D006830:Hydralazine; D003000:Clonidine; C006153:budralazine