title: Dose-dependent effects of L-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats.
abstract: The physiological function of L-carnosine (beta-alanyl-L-histidine) synthesized in mammalian muscles has been unclear. Previously, we observed that intravenous (i.v.) injection of L-carnosine suppressed renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats, and L-carnosine administered via the diet inhibited the elevation of blood pressure (BP) in deoxycorticosterone acetate salt hypertensive rats. To identify the mechanism, we examined effects of i.v. or intralateral cerebral ventricular (l.c.v.) injection of various doses of L-carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (1 microg i.v.; 0.01 microg l.c.v.) of L-carnosine significantly suppressed RSNA and BP, whereas higher doses (100 microg i.v.; 10 microg l.c.v.) elevated RSNA and BP. Furthermore, we examined effects of antagonists of histaminergic (H1 and H3) receptors on L-carnosine-induced effects. When peripherally and centrally given, thioperamide, an H3 receptor antagonist, blocked RSNA and BP decreases induced by the lower doses of peripheral L-carnosine, whereas diphenhydramine, an H1 receptor antagonist, inhibited increases induced by the higher doses of peripheral L-carnosine. Moreover, bilateral lesions of the hypothalamic suprachiasmatic nucleus eliminated both effects on RSNA and BP induced by the lower (1 microg) and higher (100 microg) doses of peripheral L-carnosine. These findings suggest that low-dose L-carnosine suppresses and high-dose L-carnosine stimulates RSNA and BP, that the suprachiasmatic nucleus and histaminergic nerve are involved in the activities, and that L-carnosine acts in the brain and possibly other organs.
authors.affiliation: Division of Protein Metabolism, Institute for Protein Research, Osaka University, Osaka, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanida
authors.forename: Akira
authors.initials: A
authors.lastname: Niijima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Hajime
authors.initials: H
authors.lastname: Sawai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: Jiao
authors.initials: J
authors.lastname: Shen
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kiso
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagai
mesh_terms: D018681:Anesthetics, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002336:Carnosine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014520:Urethane
chemical_list: D018681:Anesthetics, General; D014520:Urethane; D002336:Carnosine