Nishimura M, Ohtsuka K, Nanbu A, Takahashi H, Yoshimura M
Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
Am J Physiol. 1998 Mar;274(3):R635-44. doi: 10.1152/ajpregu.1998.274.3.R635.
To determine the possible involvement of brain amiloride-sensitive Na+ channels in Na(+)-induced hypertension, we investigated the effects of benzamil hydrochloride, a specific blocker of these Na+ channels, on the acute pressor mechanisms of intracerebroventricular infusion of hypertonic NaCl and the continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous hypertensive rats, and of non-Na(+)-induced 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 Na+ concentrations at intracerebroventricular infusion of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-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.kg-1.day-1) for 7 days affected neither arterial pressure nor urinary excretion of vasopressin and norepinephrine in either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+ channels are expected to function as one of the Na+ receptors in the brain and to be involved in the pressor mechanism of Na(+)-induced hypertension.
为了确定脑内对氨氯地平敏感的钠通道是否可能参与钠诱导的高血压，我们研究了这些钠通道的特异性阻滞剂盐酸苯扎米尔对脑室内注入高渗氯化钠的急性升压机制以及钠诱导的慢性高血压（如醋酸脱氧皮质酮-盐性高血压或易中风自发性高血压大鼠）和非钠诱导的高血压（如肾血管性高血压大鼠）的持续升压机制的影响。在脑室内注入1.5 M高渗氯化钠时，脑室内预先注射苯扎米尔（1或10 nmol/kg）可消除脑脊液钠浓度急性升高所诱导的平均动脉压、心率、腹部交感神经放电和血浆血管升压素浓度的增加。在醋酸脱氧皮质酮-盐性和易中风自发性高血压大鼠中，连续7天脑室内注入苯扎米尔（1或10 nmol·kg⁻¹·天⁻¹）可减轻钠诱导的慢性高血压，同时伴有血管升压素和去甲肾上腺素尿排泄量的减少，但在肾血管性高血压大鼠中则无此现象。在两种高血压模型中，静脉输注苯扎米尔（10 nmol·kg⁻¹·天⁻¹）7天对动脉压以及血管升压素和去甲肾上腺素的尿排泄均无影响。预计可被苯扎米尔阻断的脑内对氨氯地平敏感的钠通道可作为脑内钠受体之一发挥作用，并参与钠诱导的高血压的升压机制。
