Effect of endotoxin on the angiotensin II receptor in cultured vascular smooth muscle cells.
1. In some tissues, a decrease in the number of cell surface receptors and alterations of the receptor coupling have been proposed as possible mechanisms mediating the deleterious effects of bacterial endotoxin in septic shock. 2. The effects of bacterial lipopolysaccharide (Escherichia coli 0111-B4; LPS) on vascular angiotensin II and vasopressin receptors have been examined in cultured aortic smooth muscle cells (SMC) of the rat by use of radioligand binding techniques. 3. In vascular SMC exposed to 1 micrograms ml-1 endotoxin for 24 h, a significant increase in angiotensin II binding was found. The change in [125I]-angiotensin II binding corresponded to an increase in the number of receptors whereas the affinity of the receptors was not affected by LPS. In contrast, no change in [3H]-vasopressin binding was observed. 4. The pharmacological characterization of angiotensin II binding sites in control and LPS-exposed cells demonstrated that LPS induced an increase in the AT1 subtype of the angiotensin II receptors. Receptor coupling as evaluated by measuring total inositol phosphates was not impaired by LPS. 5. The effect of LPS on the angiotensin II receptor was dose-, time- and protein-synthesis dependent and was associated with an increased expression of the receptor gene. 6. The ability of LPS to increase angiotensin II binding in cultured vascular SMC was independent of the endotoxin induction of NO-synthase. 7. These results suggest that, besides inducing factors such as cytokines and NO-synthase, endotoxin may enhance the expression of cell surface receptors. The surprising increase in angiotensin II binding in LPS exposed VSM cells may represent an attempt by the cells to compensate for the decreased vascular responsiveness. It may also result from a non-specific LPS-related induction of genes.
Burnier
M
M
Division of Hypertension, CHUV, Lausanne, Switzerland.
Centeno
G
G
Waeber
G
G
Centeno
C
C
Bürki
E
E
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000187:drug effects*; D017483:Receptors, Vasopressin / Q000096:biosynthesis / Q000187:drug effects; D013268:Stimulation, Chemical
D004731:Endotoxins; D007295:Inositol Phosphates; D008070:Lipopolysaccharides; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D000804:Angiotensin II; D012313:RNA; C044101:endotoxin, Escherichia coli; D006152:Cyclic GMP