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(Hypertension. 2000;35:443.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Role of FMRFamide-Activated Brain Sodium Channel in Salt-Sensitive Hypertension

Masato Nishimura; Ken Ohtsuka; Hakuo Takahashi; Manabu Yoshimura

From the Department of Clinical and Laboratory Medicine (M.N., K.O., M.Y.), Kyoto Prefectural University of Medicine, Kamikyo-ku, Kyoto, Japan; and Department of Clinical Sciences and Laboratory Medicine (H.T.), Kansai Medical University, Moriguchi City, Osaka, Japan.

Correspondence to Masato Nishimura, MD, Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan. E-mail nishim{at}labmed.kpu-m.ac.jp

Abstract—FMRFamide, a cardioexcitatory neuropeptide, directly activates a newly cloned amiloride-sensitive sodium channel that is expressed specifically in the brain and blocked by benzamil hydrochloride. In the present study, we investigated the effects of short- and long-term intracerebroventricular infusion of FMRFamide on arterial pressure, sympathetic activity, vasopressin release, and brain renin-angiotensin system genes in rats and studied the role of FMRFamide-activated brain sodium channels in salt-sensitive hypertension. The intracerebroventricular preinjection of FMRFamide and subsequent intracerebroventricular infusion of 0.15 mol/L NaCl increased mean arterial pressure (FMRFamide: 30 nmol/kg +13±2.6 mm Hg, P<0.01; 100 nmol/kg +21±1.8 mm Hg, P<0.01), heart rate, abdominal sympathetic activity, and plasma vasopressin concentration compared with vehicle. The intracerebroventricular copreinjection with either benzamil or CV-11974 abolished these increases. In rats administered a high-salt diet (8% NaCl), the continuous intracerebroventricular infusion of FMRFamide (50 and 200 nmol · kg^-1 · d^-1) for 5 days increased mean arterial pressure, heart rate, urinary excretion of vasopressin and norepinephrine, and mRNAs of renin, angiotensin I–converting enzyme, and angiotensin II type 1 receptor in hypothalamus and brain stem compared with vehicle. These increases were abolished by intracerebroventricular coinfusion of benzamil. In rats administered a low-salt diet (0.3% NaCl), however, increases in these variables were smaller than those in rats receiving a high-salt diet. Together, these findings suggest that brain FMRFamide-activated sodium channels may be involved in the mechanism of salt-sensitive hypertension through regulation of the brain renin-angiotensin system.

Key Words: hypertension, sodium-dependent • renin-angiotensin system • brain • nervous system, sympathetic

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