fmrfamide and Hypertension

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.

Topics: Animals; Blood Pressure; Cerebral Ventricles; Dose-Response Relationship, Drug; FMRFamide; Hypertension; Male; Membrane Transport Modulators; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Saline Solution, Hypertonic

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.

Topics: Amiloride; Anesthesia; Animals; Arginine Vasopressin; Blood Pressure; Brain Chemistry; DNA Primers; FMRFamide; Ganglia, Sympathetic; Gene Expression; Heart Rate; Hypertension; Injections, Intraventricular; Male; Norepinephrine; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Renin; Renin-Angiotensin System; RNA, Messenger; Sodium Channels; Sodium Chloride, Dietary

The effect of several synthetic FMRF-like peptides in hemodynamics and tonus of isolated rat vessels was studied. Peptide pGlu-Aps-Pro-Phe-Leu-Arg-Phe-NH2 and its C-terminal fragment Arg-Phe-NH2 induced i.v. short-term increase in arterial blood pressure and heart rate in narcotized rats. Benzpgexonium could reduce both effects of the drug. The peptide effect on blood pressure could be neutralized by prazosin; tachycardia could be prevented by propranolol. The studied peptide and its C-end tetra-, penta- and dipeptide produced relaxation of isolated rat aorta toned by prostaglandin F2 alpha. It is supposed that hypertensive effect of FMRF-like peptides is realized through central mechanisms.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Culture Media; FMRFamide; Helix, Snails; Hypertension; In Vitro Techniques; Male; Neuropeptides; Oligopeptides; Rats; Rats, Inbred Strains; Tissue Extracts