Benzamil blockade of brain Na1 channels averts Na1-induced hypertension in rats

Nishimura, Masato, Ken Ohtsuka, Akira Nanbu, Hakuo Takahashi, and Manabu Yoshimura. Benzamil blockade of brain Na1 channels averts Na1-induced hypertension in rats. Am. J. Physiol. 274 (Regulatory Integrative Comp. Physiol. 43): R635–R644, 1998.—To determine the possible involvement of brain amiloride-sensitive Na1 channels in Na1-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na1 channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na1-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na1induced hypertension, such as renovascular hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10 nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal sympathetic discharge, and plasma vasopressin concentration induced by an acute increase in cerebrospinal Na1 concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol ·kg21 ·day21) for 7 days attenuated Na1-induced chronic hypertension in both deoxycorticosterone acetate-salt and stroke-prone spontaneous hypertensive rats, accompanied by reduction of urinary excretion of vasopressin and norepinephrine but not in renovascular hypertensive rats. Intravenous infusion of benzamil (10 nmol ·kg21 ·day21) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na1 channels are expected to function as one of the Na1 receptors in the brain and to be involved in the pressor mechanism of Na1-induced hypertension.