Effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhage in conscious rats.
We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Sirén: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 ml/300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a minithermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to saline-treated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 ml/300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.
Feuerstein
G
G
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Sirén
A L
AL
Goldstein
D S
DS
Johnson
A K
AK
Zerbe
R L
RL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014667:Vasopressins / Q000097:blood
D002395:Catecholamines; D014667:Vasopressins; D009020:Morphine; D012083:Renin