Effect of endotoxin on the angiotensin II receptor in cultured vascular smooth muscle cells

Burnier, Michel; Centeno, Gabriel; Waeber, Gérard; Centeno, Catherine; Bürki, E.

doi:10.1111/j.1476-5381.1995.tb15105.x

Cited by 14 publications

(12 citation statements)

References 37 publications

(40 reference statements)

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“…Endotoxin can alter receptor function directly (91) or indirectly via cytokines, NO, and PKC. No change in either the number or affinity of V 1 Rs was seen in cultured aortic smooth muscle cells exposed to lipopolysaccharide for 24 hrs, however (92).…”

Section: Changes In Vasopressin Receptor Behaviormentioning

confidence: 77%

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

Barrett

Singer²,

Clapp³

2007

Critical Care Medicine

199

129

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The pathophysiologic mechanism underlying vasopressin hypersensitivity in septic shock is probably multifactorial. It is doubtful that this phenomenon is merely the consequence of replacing a deficiency. Changes in vascular receptors or their signaling and/or interactions between vasopressin, nitric oxide, and adenosine triphosphate-dependent potassium channels are likely to be relevant. Further translational research is required to improve our understanding and direct appropriate educated clinical use of vasopressin.

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Section: Changes In Vasopressin Receptor Behaviormentioning

confidence: 77%

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

Barrett

Singer²,

Clapp³

2007

Critical Care Medicine

199

129

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“…The receptor binding assay was conducted either on intact rat smooth muscle cells solely expressing the angiotensin II AT1 receptor subtype (Burnier et al, 1995) or on membrane preparations obtained from the same cells.…”

Section: Radioligand Binding Studiesmentioning

confidence: 99%

In Vitro and in Vivo Characterization of the Activity of Telmisartan: An Insurmountable Angiotensin II Receptor Antagonist

Maillard¹,

Perregaux²,

Centeno³

et al. 2002

J Pharmacol Exp Ther

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In vitro studies have shown that telmisartan is an insurmountable angiotensin II subtype-1 (AT1) receptor antagonist. Herein, the molecular basis of this insurmountable antagonism has been investigated in vitro, and the effect of telmisartan has been compared in vivo with that of irbesartan and candesartan. Association and dissociation kinetics of telmisartan to AT1 receptors have been characterized in vitro on rat vascular smooth muscle cells (RVSMC) expressing solely the AT1 receptor subtype. In a second set of experiments, the antagonistic efficacy of single intravenous doses (0.1, 0.3, and 1 mg/kg) of telmisartan was compared with that of irbesartan (0.3, 1.0, 3.0, and 10.0 mg/kg) and candesartan (0.3 and 1 mg/kg) in conscious, normotensive, male Wistar rats. The results show that the specific binding of [ 3 H]telmisartan to the surface of living RVSMC is saturable and increases quickly to reach equilibrium within 1 h. Telmisartan dissociates very slowly from the receptor with a dissociation half-life (t 1/2 ) of 75 min, which is comparable with candesartan and almost 5 times slower than angiotensin II (AngII). In vivo, telmisartan blunts the blood pressure response to exogenous AngII dose dependently. The blockade is long lasting and remains significant at 24 h at doses Ͼ0.1 mg/kg. Ex vivo assessment of the AT1 receptor blockade using an in vitro AngII receptor binding assay shows similar results. When administered intravenously in rats, telmisartan is 10-fold more potent than irbesartan and comparable to candesartan. Taken together, our in vitro data show that the insurmountable antagonism of telmisartan is due at least in part to its very slow dissociation from AT1 receptors.

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“…Increased Ang II binding in cultured vascular smooth muscle cells has been reported after incubation with endotoxin. 15 Differential effects of proinflammatory cytokines on Ang II binding and AT 1 mRNA in vascular smooth muscle cells have been shown. In this context, it has been reported that interleukin-1␣ (IL-1␣) but not tumor necrosis factor-␣ (TNF-␣) or interferon-␥ (IFN-␥) increases Ang II binding and AT 1 mRNA levels, whereas the combination of IL-1␣, TNF-␣, and IFN-␥ decreases Ang II binding.…”

mentioning

confidence: 99%

Downregulation of Angiotensin II Type 1 Receptors During Sepsis

et al. 2001

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Abstract-Our study aimed to characterize the mechanisms underlying the attenuated cardiovascular responsiveness toward the renin-angiotensin system during sepsis. For this purpose, we determined the effects of experimental Gram-negative and Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous upregulation of NO synthase isoform II expression and to pronounced hypotension. Despite increased plasma renin activity and plasma angiotensin (Ang) II levels, plasma aldosterone concentrations were normal, and the blood pressure response to exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of blood pressure during sepsis by short-term infusion of the NO donor sodium nitroprusside in normal rats did not alter their blood pressure response to exogenous Ang II. Therefore, we considered the possibility of an altered expression of Ang II receptors during sepsis. It turned out that Ang II type 1 receptor expression was markedly downregulated in all organs of septic rats. Further in vitro studies with rat renal mesangial cells showed that NO and a combination of proinflammatory cytokines (interleukin-1␤, tumor necrosis factor-␣, and interferon-␥) downregulated Ang II type 1 receptor expression in a synergistic fashion. In summary, our data suggest that sepsis causes a systemic downregulation of Ang II type 1 receptors that is likely mediated by proinflammatory cytokines and NO. We suggest that this downregulation of Ang II type 1 receptors is the main reason for the attenuated responsiveness of blood pressure and of aldosterone formation to Ang II and, therefore, contributes to the characteristic septic shock. (Hypertension. 2001;38:177-182.)

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Effect of endotoxin on the angiotensin II receptor in cultured vascular smooth muscle cells

Cited by 14 publications

References 37 publications

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

In Vitro and in Vivo Characterization of the Activity of Telmisartan: An Insurmountable Angiotensin II Receptor Antagonist

Downregulation of Angiotensin II Type 1 Receptors During Sepsis

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