Role of FMRFamide-activated brain sodium channel in salt-sensitive hypertension.

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.

• Authors: M Nishimura, K Ohtsuka, H Takahashi, M Yoshimura
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 35 Issue 1 Pt 2 Pg. 443-50 (Jan 2000) ISSN: 0194-911X [Print] United States
• PMID: 10642339 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• RNA, Messenger
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin
• Sodium Channels
• Sodium Chloride, Dietary
• benzamil
• Arginine Vasopressin
• FMRFamide
• Amiloride
• Peptidyl-Dipeptidase A
• Renin
• Norepinephrine

Topics

• Amiloride (analogs & derivatives, pharmacology)
• Anesthesia
• Animals
• Arginine Vasopressin (blood, urine)
• Blood Pressure (drug effects)
• Brain Chemistry (drug effects, genetics)
• DNA Primers
• FMRFamide (pharmacology, urine)
• Ganglia, Sympathetic (chemistry, drug effects, enzymology)
• Gene Expression (drug effects)
• Heart Rate (drug effects)
• Hypertension (physiopathology)
• Injections, Intraventricular
• Male
• Norepinephrine (urine)
• Peptidyl-Dipeptidase A (genetics)
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Receptors, Angiotensin (genetics)
• Renin (genetics)
• Renin-Angiotensin System (physiology)
• Sodium Channels (physiology)
• Sodium Chloride, Dietary (pharmacology)