| Co-Investigator(Kenkyū-buntansha) |
HANO Takuzo Wakayama Medical University, School of Medicine, Associate Professor, 助教授 (90156381)
TSURUO Yoshihiro Wakayama Medical University, School of Medicine, Professor, 教授 (90207449)
SHIRASAWA Nobuyuki Yamagata University, School of Medicine, Associate Professor, 医学部, 助教授 (40133392)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
Emotional or physical stress triggers Tako-tsubo cardiomyopathy in postmenopausal female, which is characterized by elevation of ST segment in the ECG and left ventricular apical ballooning in the LVG. We succeeded to mimic this cardiac attack using immobilization stress (IMO) of rats, a well-known animal model of emotional stress. IMO-induced cardiac changes are completely cancelled by pretreatment with combined blockade of α- and β-adrenoceptors, suggesting that exaggerated sympatho-adrenomedullary outflow is involved in the cardiac change. To study whether these cardiac changes are especially predominant in elderly female subjects, we compared cardiac function and the induction of c-fos mRNA or c-Fos- immunoreactive(IR) in the heart or the brain in response to IMO between ovariectomized rats with placebo treatment (OVX+P) and ovariectomized rats supplemented with b-estradiol (OVX+E).
1.In OVX+P rats, % contraction in LVG was significantly reduced in response to stress, whole it was n
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ot significantly changed in OVX+E rats. In both groups, heart rate was significantly increased in response to stress. However, heart rate in stress was significantly higher in OVX+P than in OVX+E.
2.Expression of c-fos mRNA in the heart and paraventricular hypothalamic nucleus in response to IMO was attenuated in OVX+E.
3.Innervation of catechoraminergic nerve fibers was reduced in OVX+E.
4.Increased c-Fos-IR cells in response to IMO were observed in cerebral cortex, septum, thalamus, hypothalamus, midbrain, pons and medulla oblongata in accordance with previous findings. In OVX+E compared with OVX+P, the numbers of c-Fos-IR cells were significantly lower in the lateral septum, paraventricular hypothalamic nucleus, dorsomedial hypothalamic nucleus, medial amygdaloid nucleus, lateral periaqueductal gray, laterodorsal, tegmental nucleus and locus coeruleus, while they were significantly higher in paraventricular thalamic nucleus and nucleus of the solitary tract. These data suggest that neuronal activity in these areas is influenced by systemic estrogen level.
Taken together, estrogen attenuates the stress response in the central nervous system and cardiac tissues. In turn, reduction of estrogen may underline the high incidence of stress-induced Tako-tsubo carrdiomyopathy in postmenoausal female. Less
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