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.