CONTRIBUTION OF THE CENTRAL NERVOUS SYSTEM TO THE ACTION OF SEVERAL ANTIHYPERTENSIVE AGENTS (METHYLDOPA, HYDRALAZINE AND GUANETHIDINE)

¹ Cardiovascular Pharmacology Section, Wyeth Laboratories Inc., Radnor, Pennsylvania
² Cardiovascular Pharmacology Section, Wyeth Laboratories Inc., Radn or, Pennsylvania

The central nervous system offers a potential site of action for the reduction of blood pressure and has been implicated in activity of several clinically used antihypertensive agents. The role of the central nervous system in the depressor response to methyldopa, hydralazine and guanethidine was evaluated in renal hypertensive rats in the present study. The agents were administered orally, twice daily, for three and one-half days at two or more doses. Blood pressures were determined before and after treatment. The animals then were anesthetized and the activity of one lumbar sympathetic chain was recorded. All drugs induced dose-related decreases in blood pressure. Methyldopa inhibited spontaneous sympathetic outflow greatly. Hydralazine also tended to reduce sympathetic firing, but only the effect of the lower dose attained statistical significance. Guanethidine did not influence the level of sympathetic activity. Cardiovascular reflexes could be activated in all groups but the magnitude of the nerve response was influenced by pretreatment particularly by the high dose of methyldopa. These experiments suggest that reduction of sympathetic outflow contributes importantly to the antihypertensive action of methyldopa but only to a much more limited extent to that of hydralazine.