[Antihypertensive effect of guanfacine in rats]

Effects of an antihypertensive drug, guanfacine, on blood pressure and heart rate were studied in comparison with findings in a related drug, clonidine. Conscious rats (normotensive rat, SHR, DOCA-hypertensive rat and renal hypertensive rat), anesthetized rats and pithed rats were used. Effects of guanfacine resembled those of clonidine but were about 10 times less potent. Both drugs produced an initial transient increase in blood pressure and a prolonged decrease then followed. In the SHR, a decrease in blood pressure occurred. The vasopressor effect of guanfacine was inhibited by phentolamine (1 mg/kg i.v.) and potentiated after previous treatment of the rats with reserpine (5 mg/kg i.p. 24 hr prior to drug administration, indicating that the effect was produced through activation of peripheral alpha-adrenoceptors. The vasodepressor effect of guanfacine was clearly dose-dependent, and was more marked when the initial level of the blood pressure was high, while that of clonidine was dose-dependent, only within a limited dosage range. Vasodepressor effects of guanfacine were associated with a decrease in the efferent discharges of the renal sympathetic nerve. Guanfacine, when given intracisternally produced a greater fall of blood pressure and a greater inhibition of the renal nerve activity than when given intravenously. It is concluded that the antihypertensive effects of guanfacine are due to stimulation of alpha-adrenoceptors within the central nervous system.