Dose-different effects of orexin-A on the renal sympathetic nerve and blood pressure in urethane-anesthetized rats.
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 H(3)-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 H(1)-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.
Tanida
Mamoru
M
Institute for Protein Research, Osaka University, 3-2, Yamadaoka, Suita, Osaka 565-0871, Japan. tanida.m@protein.osaka-u.ac.jp
Niijima
Akira
A
Shen
Jiao
J
Yamada
Shigeru
S
Sawai
Hajime
H
Fukuda
Yutaka
Y
Nagai
Katsuya
K
D018686:Anesthetics, Intravenous; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002552:Cerebral Ventricles / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017442:Histamine Agonists / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009479:Neuropeptides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000068797:Orexins; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014520:Urethane / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D017442:Histamine Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010880:Piperidines; D014520:Urethane; C052075:thioperamide