Role of FMRFamide-activated brain sodium channel in salt-sensitive hypertension.
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.
Nishimura
M
M
Department of Clinical and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kamikyo-ku, Kyoto, Japan. nishim@labmed.kpu-m.ac.jp
Ohtsuka
K
K
Takahashi
H
H
Yoshimura
M
M
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D017931:DNA Primers; D019835:FMRFamide / Q000494:pharmacology* / Q000652:urine; D005728:Ganglia, Sympathetic / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D015222:Sodium Channels; D017673:Sodium Chloride, Dietary; C013407:benzamil; D001127:Arginine Vasopressin; D019835:FMRFamide; D000584:Amiloride; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D009638:Norepinephrine