| Research Abstract |
FMRFamide, a cardioexcitatory neuropeptide, directly activates a newly-cloned amiloride-sensitive sodium channel which is expressed specifically in the brain and blocked by benzamil hydrochloride. In the present study, we investigated the effects of acute and chronic intracerebroventricular (ICV) 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. ICV preinjection of FMRFamide and subsequent ICV infusion of 0.15 M 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 as compared with vehicle. ICV co-preinjection with either benzamil or CV-11974 abolished these increases. In rats given a high-salt diet (8% NaCl), continuous ICV infusion of FMRFamide (50,200 nmol/kg/d) for 5 days increased mean arterial pressure, heart rate, urinary excretion of vasopressin and norepinephrine, and mRNAs of renin, angiotensin I-converting enzyme and AT1 receptor in hypothalamus and brainstem as compared with vehicle. These increases were abolished by ICV co-infusion of benzamil. In rats given a low-salt diet (0.3% NaCl), however, increases in these variables were smaller than in high-salt rats. 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.
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