Effects of hydralazine on cardiac responsiveness to adrenergic agonists in streptozotocin-induced diabetic rats.

The present investigation was undertaken to study the effects of hydralazine treatment (50 mg/kg/day, p.o.) on methoxamine and isoproterenol-induced responses in cardiac preparations of control and streptozotocin (STZ)-induced diabetic rats. Triiodothyronine (T3) and thyroxine (T4) levels were found to be significantly decreased in diabetic rats and this decrease was prevented by hydralazine treatment. Methoxamine and isoproterenol produced a dose-dependent positive chronotropic and positive inotropic effect in right and left atrium respectively. These responses to methoxamine were significantly increased, whereas, those to isoproterenol were significantly decreased in preparations obtained from diabetic rats. Hydralazine treatment did not alter the isoproterenol-induced chronotropic effect in right atrium. However, it prevented the diabetes-induced increase in responsiveness to methoxamine in this preparation. Hydralazine increased significantly the inotropic response to methoxamine and isoproterenol in left atrium of control and diabetic rats. Both the pD2 value and maximum response were increased. The studies indicates that hydralazine-induced alterations in the responsiveness to methoxamine could partly be due to its ability to prevent diabetes-induced hypothyroidism. The effects of hydralazine on isoproterenol-induced responses appear to be independent of hypothyroidism, and some post-receptor mechanisms and metabolic derangements might be responsible for this effect.