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Cardiovascular effects of centrally acting orexin A in haemorrhage-shocked rats

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Jochem J., Zwirska-Korczala K., Zabielski R., Kato I., Kuwahara A.

Journal of Physiology and Pharmacology. Supplement

2006

tom 57

nr 11

115-124

Orexin A influences the central cardiovascular regulation, since after intracerebroventricular (icv) administration it evokes short-lasting increases in mean arterial pressure (MAP) and heart rate (HR) in normotensive animals. The aim of the present study was to examine haemodynamic effects of orexin A in haemorrhage-shocked rats. Experiments were carried out in anaesthetized Wistar rats subjected for a critical irreversible haemorrhagic hypotension of 20-25 mmHg, which resulted in the death of all saline icv-treated control animals within 30 min. Orexin A (0.5-1.5 nmol; icv) administered at 5 min of critical hypotension evoked dose-dependent long-lasting increases in MAP, HR and renal, mesenteric and hindquarters blood flows, with a 100% survival of 2 h after treatment (1.5 nmol; icv). Changes in MAP and peripheral haemodynamics were inhibited by intravenous pretreatment with alpha1- and alpha2-adrenoceptor antagonists prazosin (0.5 mg/kg) and yohimbine (1.0 mg/kg), respectively. Moreover, both antagonists significantly decreased the survival rate to 16.6 and 33.3% (P<0.05 vs. orexin A [1.5 nmol]-treated group). In contrast, ß-adrenoceptor antagonist propranolol (1.0 mg/kg) completely blocked orexin A-induced HR changes, without influence on MAP, peripheral blood flows and the survival rate. Therefore, we conclude that centrally acting orexin A evokes the resuscitating effect in haemorrhage-shocked rats due to the activation of the sympathetic nervous system.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology. Supplement

1 Jochem J.

1 Kato I.

1 Kuwahara A.

1 Zabielski R.

1 Zwirska-Korczala K.

1 2006

Wyniki wyszukiwania

Cardiovascular effects of centrally acting orexin A in haemorrhage-shocked rats