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ORIGINAL RESEARCH ARTICLE

Dose-Different Effects of Orexin-A on the Renal Sympathetic Nerve and Blood Pressure in Urethane-Anesthetized Rats

Mamoru Tanida^*,1, Akira Niijima, Jiao Shen^*, Shigeru Yamada^*, Hajime Sawai, Yutaka Fukuda and Katsuya Nagai^*

^* Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan; Niigata University School of Medicine, Asahimachidoori, Niigata 951-8122, Japan; and Department of Physiology and Biosignaling, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan

To whom requests for reprints should be addressed at ¹ Institute for Protein Research, Osaka University, 3-2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: tanida.m{at}protein.osaka-u.ac.jp

Previous studies have demonstrated that central injection of orexin-A affects renal sympathetic nerve activity (RSNA) and blood pressure (BP) in both anesthetized and unanesthetized rats. In the present study, we examined, using urethane-anesthetized rats, the dose-dependent effects of intravenous (iv) or intralateral cerebral ventricular (LCV) injection of various doses of orexin-A on RSNA and BP. We found that injection of a low dose of orexin-A (10 ng iv or 0.01 ng LCV) suppressed RSNA and BP significantly. Conversely, a high dose (1000 ng iv or 10 ng LCV) of orexin-A elevated both RSNA and BP significantly. Pretreatment with either iv or LCV injection of thioperamide, a histaminergic H₃-receptor antagonist, eliminated the effects of a low dose of orexin-A on both RSNA and BP. Both iv and LCV injection of diphenhydramine, a histaminergic H₁-receptor antagonist, abolished the effects of a high dose of orexin-A on RSNA and BP. Furthermore, bilateral lesions of the hypothalamic suprachiasmatic nucleus (SCN) abolished the effects of both low and high doses of orexin-A on RSNA and BP. These findings suggest that orexin-A affects RSNA and BP in a dose-dependent manner and that the SCN and histaminergic nerve may be involved in the dose-different effects of orexin-A in rats.

Key Words: autonomic nerve • suprachiasmatic nucleus • histaminergic nerve • thioperamide • diphenhydramine

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