The vascular response to adrenergic stimulation in pithed rats following endotoxin.
In vivo and in vitro studies have shown that the vascular response to catecholamine is attenuated during endotoxemia. The mechanism of such attenuation is complex and might involve high catecholamine-induced desensitization of adrenoceptors. The purpose of this study was to assess the vascular response to adrenergic stimulation after endotoxin (ETX) administration in pithed rats. In pithed rats, sympathetic outflow is controlled by stimulation, ETX does not elevate norepinephrine (NE), and there are no compensatory reflexes. Rats were pithed, curarized, and adrenal-demedullated. Preganglionic thoracolumbar nerves were stimulated (3 Hz, 10 V, 0.5 msec) for 1 hr after pithing, at which time the first set of frequency and NE-dose responses were assessed by measuring the peak increase in diastolic blood pressure. Intravenous ETX (1.5 mg/kg or 0.5 mg/kg) or saline was administered immediately after these measurements. A sham group was designed to mimic the falling blood pressure pattern seen in the endotoxin group during 1 hr after ETX was given by gradually decreasing the stimulation frequency. The second set of frequency and NE-dose responses were evaluated 1 hr after ETX, saline, or sham treatment. Plasma NE and epinephrine (EPI) were determined before and 1 hr after ETX (1.5 mg/kg) or saline injection. The results showed that blood pressure response to adrenergic stimulation was markedly attenuated in pithed rats following both high and low doses of ETX compared with the saline and sham groups. Plasma NE was not elevated by ETX insult in pithed rats. We propose that mechanisms other than high-catecholamine-induced adrenergic desensitization or hypotension account for the attenuated adrenergic responsiveness of the vasculature following ETX.
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois.
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Zhou
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Jones
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000502:physiology* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000502:physiology* / Q000601:surgery; D013564:Sympathetic Nervous System / Q000502:physiology
D004731:Endotoxins; D009638:Norepinephrine; D004837:Epinephrine