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

J Physiol Pharmacol. 2006 Nov:57 Suppl 11:115-24.

Abstract

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.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Cardiovascular System / drug effects*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Humans
  • Hypotension / etiology
  • Hypotension / metabolism
  • Hypotension / physiopathology
  • Injections, Intraventricular
  • Intracellular Signaling Peptides and Proteins / administration & dosage
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Male
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacology*
  • Neuropeptides / physiology
  • Orexins
  • Prazosin / pharmacology
  • Propranolol / pharmacology
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Shock, Hemorrhagic / complications
  • Shock, Hemorrhagic / metabolism
  • Shock, Hemorrhagic / physiopathology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiopathology
  • Sympathomimetics / administration & dosage
  • Sympathomimetics / pharmacology*
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Sympathomimetics
  • Yohimbine
  • Propranolol
  • Prazosin