Attenuated defense response and low basal blood pressure in orexin knockout mice 

作成者 萱場, 祐司, 中村, 晃, 粕谷, 善俊, 大内, 崇史, 柳沢, 正史, 小室, 一成, 福田, 康一郎, 桑木, 共之
作成者の別表記 Kayaba, Yuji, Nakamura, Akira, Kasuya, Yoshitoshi, Ohuchi, Takashi, Yanagisawa, Masashi, Komuro, Issei, Fukuda, Yasuichiro, Kuwaki, Tomoyuki
キーワード等 hypothalamus, stress, respiration, sympathetic nervous system, circadian rhythm
日本十進分類法 (NDC) 491.3
内容 The perifornical area of the hypothalamushas been known as the center for the defense response, or "fight or flight" response, which is characterized by aconcomitant rise in arterial blood pressure (AP), heart rate (HR), and respiratory frequency (Rf). We examined whetherorexin, a recently identified hypothalamic neuropeptide, contributesto the defense response and basal cardiovascularregulation using orexin knockout mice. Microinjection of aGABA-A receptor antagonist, bicuculline methiodide (0.1–1 mM in 20 nl), to the perifornical area in urethane-anesthetizedwild-type mice elicited dose-dependent increases in AP,HR, and Rf. Although similar changes were observed inorexin knockout mice, intensities were smaller and durationwas shorter than those in wild-type mice. Moreover, in anawake and freely moving condition, telemeter-indwellingorexin knockout mice showed diminished cardiovascular andbehavioral responses to emotional stress in the residentintrudertest. We also found that basal AP in orexin knockoutmice was significantly lower in both anesthetized (117+-8mmHg in wild type and 92+-3 in knockout) and conscious(125+-6 mmHg in wild type and 109+-2 in knockout) conditions.Alpha-Adrenergic blockade with prazosin or ganglion blockadewith hexamethonium canceled the difference in basal AP. HRand cardiac contractile parameters by echocardiography did notdiffer between the two strains of mice. These results indicatelower sympathetic vasoconstrictor tone in knockout mice. Thepresent study suggests that orexin-containing neurons in theperifornical area play a role as one of the efferent pathways ofdefense response and also operate as a regulator of AP at basalcondition by activating sympathetic outflow.
コンテンツの種類 雑誌掲載論文 Journal Article
DCMI資源タイプ text
掲載誌情報 American Journal of Physiology Regulatory Integral and Comparative Physiology Vol.285 no.3 page.R581-R593 (200309)
言語 英語
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