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Stress‐Specific Opioid Modulation Of Haemodynamic Counter‐Regulation
Author(s) -
Molina Patricia E
Publication year - 2002
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2002.03638.x
Subject(s) - naltrexone , sympathetic nervous system , hemodynamics , endogenous opioid , medicine , opiate , endocrinology , blood pressure , opioid , shock (circulatory) , opioid receptor , opioid peptide , catecholamine , haemodynamic response , narcotic antagonist , anesthesia , heart rate , receptor
SUMMARY 1. The haemodynamic and cardiovascular responses to stress, in addition to being under control of the autonomic nervous system, are also under opiate modulation. Our studies have provided evidence for activation of the endogenous opioid system in haemorrhagic shock, sepsis and trauma. Furthermore, we have demonstrated that both central and systemic opiate administration to naïve rats result in marked alterations in haemodynamic responses, which are associated with activation of the sympathetic nervous system. 2. Because of the ubiquitous presence of opiate receptors in both the central nervous system and peripheral tissues, as well as their production and release centrally and peripherally, this facilitates an endocrine as well as a paracrine contribution to modulating vascular responses to stress, either directly or indirectly. Results from previous studies suggest that endogenous opioids are not involved in mediating the lipopolysacharide‐induced hypotensive response. 3. In more recent studies, we have examined the role of opiate receptor activation in modulating the haemodynamic and neuroendocrine responses to fixed pressure haemorrhagic shock in conscious unrestrained rats. Using systemic opiate blockade (naltrexone, 15 mg/kg, i.p.) prior to haemorrhage, we have observed that blood loss required to achieve mean arterial blood pressure of 40 mmHg was higher in naltrexone‐treated animals than in time‐matched saline controls. Interestingly, the haemodynamic modulation exerted by naltrexone cannot be attributed to differences in circulating catecholamine levels. Haemorrhage produced an immediate and progressive increase in circulating adrenaline and noradrenaline levels, reaching values that were 50‐ and 20‐fold higher than basal, respectively. Naltrexone pretreatment did not alter the time‐course or magnitude of the rise in circulating levels of catecholamines. 4. These results indicate that endogenous opioid activation contributes to the haemodynamic dishomeostasis associated with blood loss. Our findings suggest stress‐specific roles for opiate‐sensitive haemodynamic counter‐regulatory responses.