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

Yuji Kayaba, Akira Nakamura, Yoshitoshi Kasuya, Takashi Ohuchi, Masashi Yanagisawa, Issei Komuro, Yasuichiro Fukuda, Tomoyuki Kuwaki

Research output: Contribution to journalArticle

256 Citations (Scopus)

Abstract

The perifornical area of the hypothalamus has been known as the center for the defense response, or "fight or flight" response, which is characterized by a concomitant rise in arterial blood pressure (AP), heart rate (HR), and respiratory frequency (Rf). We examined whether orexin, a recently identified hypothalamic neuropeptide, contributes to the defense response and basal cardiovascular regulation using orexin knockout mice. Microinjection of a GABA-A receptor antagonist, bicuculline methiodide (0.1-1 mM in 20 nl), to the perifornical area in urethane-anesthetized wild-type mice elicited dose-dependent increases in AP, HR, and Rf. Although similar changes were observed in orexin knockout mice, intensities were smaller and duration was shorter than those in wild-type mice. Moreover, in an awake and freely moving condition, telemeter-indwelling orexin knockout mice showed diminished cardiovascular and behavioral responses to emotional stress in the resident-intruder test. We also found that basal AP in orexin knockout mice was significantly lower in both anesthetized (117 ± 8 mmHg in wild type and 92 ± 3 in knockout) and conscious (125 ± 6 mmHg in wild type and 109 ± 2 in knockout) conditions. α-Adrenergic blockade with prazosin or ganglion blockade with hexamethonium canceled the difference in basal AP. HR and cardiac contractile parameters by echocardiography did not differ between the two strains of mice. These results indicate lower sympathetic vasoconstrictor tone in knockout mice. The present study suggests that orexin-containing neurons in the perifornical area play a role as one of the efferent pathways of defense response and also operate as a regulator of AP at basal condition by activating sympathetic outflow.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume285
Issue number3 54-3
StatePublished - Sep 1 2003

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Knockout Mice
Hypotension
Arterial Pressure
Heart Rate
GABA-A Receptor Antagonists
Efferent Pathways
Hexamethonium
Prazosin
Urethane
Microinjections
Vasoconstrictor Agents
Neuropeptides
Psychological Stress
Ganglia
Adrenergic Agents
Hypothalamus
Echocardiography
Neurons

Keywords

  • Circadian rhythm
  • Hypothalamus
  • Respiration
  • Stress
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Physiology

Cite this

Attenuated defense response and low basal blood pressure in orexin knockout mice. / Kayaba, Yuji; Nakamura, Akira; Kasuya, Yoshitoshi; Ohuchi, Takashi; Yanagisawa, Masashi; Komuro, Issei; Fukuda, Yasuichiro; Kuwaki, Tomoyuki.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 285, No. 3 54-3, 01.09.2003.

Research output: Contribution to journalArticle

Kayaba, Yuji ; Nakamura, Akira ; Kasuya, Yoshitoshi ; Ohuchi, Takashi ; Yanagisawa, Masashi ; Komuro, Issei ; Fukuda, Yasuichiro ; Kuwaki, Tomoyuki. / Attenuated defense response and low basal blood pressure in orexin knockout mice. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2003 ; Vol. 285, No. 3 54-3.
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