Dose-dependent effects of L-carnosine on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 288; no. 2; pp. R447 - R455
• Main Authors: Tanida, Mamoru, Niijima, Akira, Fukuda, Yutaka, Sawai, Hajime, Tsuruoka, Nobuo, Shen, Jiao, Yamada, Shigeru, Kiso, Yoshinobu, Nagai, Katsuya
• Format: Journal Article
• Language: English
• Published: United States 01.02.2005
• Subjects: Anesthetics, General; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Carnosine - administration & dosage; Carnosine - blood; Carnosine - pharmacology; Dose-Response Relationship, Drug; Kidney - drug effects; Kidney - innervation; Male; Rats; Rats, Sprague-Dawley; Suprachiasmatic Nucleus - physiology; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Time Factors; Urethane
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00275.2004

1 Division of Protein Metabolism, Institute for Protein Research, Osaka University, Osaka; 2 Niigata University School of Medicine, Niigata; 3 Osaka University Graduate School of Medicine, Osaka; and 4 Institute for Health Care Science, Suntory Limited, Shimamoto, Osaka, Japan Submitted 30 April 2004 ; accepted in final form 6 October 2004 The physiological function of L -carnosine ( -alanyl- L -histidine) synthesized in mammalian muscles has been unclear. Previously, we observed that intravenous (IV) 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 IV or intralateral cerebral ventricular (LCV) injection of various doses of L -carnosine on RSNA and BP in urethane-anesthetized rats. Lower doses (1 µg IV; 0.01 µg LCV) of L -carnosine significantly suppressed RSNA and BP, whereas higher doses (100 µg IV; 10 µg LCV) 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 µg) and higher (100 µg) 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. suprachiasmatic nucleus; histaminergic nerve; autonomic nervous system; hypertension; hypotension Address for reprint requests and other correspondence: K. Nagai, Div. of Protein Metabolism, Institute for Protein Research, Osaka Univ., 3-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan (E-mail: k_nagai{at}protein.osaka-u.ac.jp )