Reduced microvascular adrenergic receptor activity due to opioids in endotoxin shock.
Arteriolar sensitivity to norepinephrine is decreased in endotoxin shock, and sympathetic activity appears altered. We have tested involvement of arteriolar opioid receptors in the response to endotoxin. Cremaster muscle arteriolar reactivity of anesthetized rats was studied using videomicroscopy. Escherichia coli endotoxin (6 mg/kg, i.v., LD100) was infused over a 1-hr period. Mean arterial pressure (Pm), frequency/diameter curves of A1, A2, and A3 arterioles to lumbar sympathetic nerve stimulation (1-16 Hz), and plasma velocity were obtained in group I at control, 30 min, and 90 min postendotoxin and in group II at control and during i.v. infusion of the opiate antagonist naltrexone (0.5 mg/kg/min) at 30 and 90 min postendotoxin. Frequency-diameter curves (percentage of control diameter) were significantly (P less than 0.05) shifted to the right postendotoxin in group I indicating reduced response to lumbar sympathetic stimulation or norepinephrine from the nerve terminals. In group II rats receiving naltrexone after endotoxin, the frequency-diameter curves were significantly (P less than 0.05) shifted to the left indicating enhanced vasoconstriction to lumbar sympathetic stimulation in comparison to control and to group I postendotoxin curves. Postendotoxin, Pm and plasma velocities decreased progressively in group I but were not changed from control in group II. Since opiate receptor blockade during endotoxin shock enhances adrenergic responses of arterioles, opiate receptor stimulation appears to suppress adrenergic receptors.
Baker
C H
CH
Department of Physiology and Biophysics, College of Medicine, University of South Florida, Tampa 33612.
Sutton
E T
ET
Zhou
Z
Z
Reynolds
D G
DG
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D004723:Endorphins; D004731:Endotoxins; D011941:Receptors, Adrenergic; D011957:Receptors, Opioid; D009271:Naltrexone