Previous data on
budralazine, 1-[2-(1,3-dimethyl-2-butenylidene)-hydrazino]-
phthalazine, has indicated that it is a direct-acting vasodilating agent that does not produce marked
tachycardia. The present study was undertaken to elucidate what effects may be seen on the central sympathetic nerve activity when
budralazine is given systemically to rats.
Budralazine (0.5, 1.0 and 5.0 mg/kg, i.v.) 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. Preganglionic adrenal sympathetic nerve activity was also reduced by
budralazine (1.0 mg/kg, i.v.). A dose of 0.5 mg/kg of
budralazine neither influenced carotid sinus nerve activity nor augmented aortic depressor nerve activity. On the contrary, a high dose of
budralazine (5.0 mg/kg) produced simultaneous increases in the heart rate and cardiac sympathetic nerve activity along with a marked suppression of aortic depressor nerve activity. Plasma
norepinephrine and
epinephrine concentrations were also increased at a dose of 5.0 mg/kg. These findings suggest that
budralazine doses of 0.5 and 1.0 mg/kg may reduce the sympathetic outflow that is mediated via central sympathoinhibitory action. Baroreceptor-mediated
tachycardia occurred after high dose
budralazine (5.0 mg/kg) administration in anesthetized rats.