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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Activation of central opioid receptors determines the timing of hypotension during acute hemorrhage-induced hypovolemia in conscious sheep

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Submitted 26 January 2006 ; accepted in final form 13 April 2006

After an initial compensatory phase, hemorrhage reduces blood pressure due to a widespread reduction of sympathetic nerve activity (decompensatory phase). Here, we investigate the influence of intracerebroventricular naloxone (opioid-receptor antagonist) and morphine (opioid-receptor agonist) on the two phases of hemorrhage, central and peripheral hemodynamics, and release of vasopressin and renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml·kg^–1·min^–1) from a jugular vein until mean arterial blood pressure (MAP) reached 50 mmHg. Starting 30 min before and continuing until 60 min after hemorrhage, either artificial cerebrospinal fluid (aCSF), naloxone, or morphine was infused intracerebroventricularly. Naloxone (200 µg/min but not 20 or 2.0 µg/min) significantly increased the hemorrhage volume compared with aCSF (19.5 ± 3.2 vs. 13.9 ± 1.1 ml/kg). Naloxone also increased heart rate and cardiac index. Morphine (2.0 µg/min) increased femoral blood flow and decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9 ± 1.5 vs. 13.9 ± 1.1 ml/kg). The effects of morphine were abolished by naloxone at 20 µg/min. It is concluded that the commencement of the decompensatory phase of hemorrhage in conscious sheep involves endogenous activation of central opioid receptors. The effective dose of morphine most likely activated µ-opioid receptors, but they appear not to have been responsible for initiating decompensation as 1) naloxone only inhibited an endogenous mechanism at a dose much higher than the effective dose of morphine, and 2) the effects of morphine were blocked by a dose of naloxone, which, by itself, did not delay the decompensatory phase.

naloxone; morphine; intracerebroventricular; vasopressin; renin

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				M. Sawdon, M. Ohnishi, R. A. Little, and E. Kirkman Naloxone does not inhibit the attenuation of the response to severe haemorrhage seen after simulated injury in the anaesthetized rat Exp Physiol, June 1, 2009; 94(6): 641 - 647. [Abstract] [Full Text] [PDF]