| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Critical Care Medicine | ||||
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 31 | ||||
| Number of Issue or Book Chapter: | 2 | ||||
| Page Range: | pp. 566-571 | ||||
| Date: | 2003 | ||||
| Institutions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehreinheit Pharmakologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz | ||||
| Identification Number: |
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| Keywords: | NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE CELLS; II TYPE-2 RECEPTOR; ANGIOTENSIN-II; SEPTIC SHOCK; ALPHA-1-ADRENERGIC RECEPTORS; CARDIAC FIBROBLASTS; RAT MODEL; SEPSIS; SUBTYPES; blood pressure; vasoplegia; mesangial cells; cytokines; nitric oxide; catecholamines | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 72425 |
Web of ScienceAbstract
Objective: The reduced pressure response to norepinephrine in septic patients has directed our interest to the regulation of alpha(1)-adrenergic receptors in vitro and in vivo during conditions mimicking acute sepsis. Design: Prospective animal trial followed by a controlled cell culture study. Setting: Laboratory of the Department of Anesthesiology. Subjects: Male Sprague-Dawley rats weighing ...
Abstract
Objective: The reduced pressure response to norepinephrine in septic patients has directed our interest to the regulation of alpha(1)-adrenergic receptors in vitro and in vivo during conditions mimicking acute sepsis. Design: Prospective animal trial followed by a controlled cell culture study. Setting: Laboratory of the Department of Anesthesiology. Subjects: Male Sprague-Dawley rats weighing 200 to 250 g and a mesangial cell line. Interventions: Experimental endotoxemia was induced in rats with lipopolysaccharide, and blood pressure dose-response studies with norepinephrine were performed. alpha(1)-Receptor gene expression was determined in various organs by a specific RNase protection assay, and tissue concentrations of the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha were measured. Rat renal mesangial cells were incubated with these cytokines or with nitric oxide donors to investigate the regulation of alpha(1)-adrenergic receptors during severe inflammation on a cellular level. Measurements and Main Results: The pressor effect of norepinephrine was markedly diminished during endotoxemia. The animals showed down-regulated mRNA levels of alpha(1A)-, alpha(1B)- and alpha(1D)-receptors in all organs investigated, and the tissue concentrations of interleukin-1beta and tumor necrosis factor-alpha were highly increased during experimental endotoxemia. Incubation of cultured rat renal mesangial cells with the cytokines resulted in diminished alpha(1B)-receptor gene expression and [H-3]prazosin binding capacity, whereas incubation of the cells with nitric oxide donors did not affect alpha(1B)-receptor expression. In line, blocking of cytokine-induced nitric oxide synthesis by coincubation of mesangial cells with N-6-nitro-L-arginine methyl ester did not influence cytokine-induced down-regulation of alpha(1B)-receptors. Conclusions: Our data show that endotoxemia causes a systemic down-regulation of alpha(1)-receptors on the level of gene expression and suggest that this effect is likely mediated by proinflammatory cytokines in a synergistic but nitric oxide-independent fashion. We propose that this down-regulation of alpha(1)-adrenergic receptors contributes to the attenuated blood pressure response to norepinephrine and, therefore, to septic circulatory failure in patients.
Metadata last modified: 19 Dec 2024 15:31
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