Cardiovascular effects of centrally acting orexin A in haemorrhage-shocked rats.
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 alpha(1)- and alpha(2)-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, beta-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.
Jochem
J
J
Department of Physiology, Medical University of Silesia, Zabrze, Poland. jjochem@poczta.onet.pl
Zwirska-Korczala
K
K
Zabielski
R
R
Kato
I
I
Kuwahara
A
A
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D000068797:Orexins; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D013566:Sympathomimetics; D015016:Yohimbine; D011433:Propranolol; D011224:Prazosin