Intracerebroventricular infusions of an amiloride analog, benzamil, reduce blood pressure in several rat models of hypertension. This effect has been attributed to an inhibition of amiloride-sensitive Na⁺ channels in the brain. This study examines whether intracerebroventricular benzamil would prevent the onset of deoxycorticosterone acetate (DOCA)-salt-induced hypertension in rats and whether this effect correlates with an inhibition of ion transport through the known amiloride-sensitive cation channels at the blood-brain barrier. We also examine whether the effects of benzamil on blood pressure are mediated by a Na⁺ channel by comparing the effects of different amiloride analogs. Benzamil (0.15 and 0.5 µg/h icv) did significantly attenuate the increase in blood pressure induced by DOCA treatment. This antihypertensive effect, however, was not associated with an alteration in a blood-brain barrier ion transport as assessed by measurements of blood-to-brain ²²Na transport and cerebral spinal fluid Na⁺ and K⁺ concentrations. Indeed, intracerebroventricular infusion of dimethyl amiloride, an amiloride analog with low affinity for Na⁺ channels, also attenuated the increase in blood pressure induced by DOCA-salt treatment. Comparisons of the effects of benzamil, dimethyl amiloride, and 3,4-dichlorobenzamil, another amiloride analog, suggest that these antihypertensive effects are mediated by an inhibition of Na⁺/Ca²⁺ exchange in the brain.

benzamil; dimethyl amiloride; dichlorobenzamil; blood pressure; brain

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