Regulation of Vascular Type 1 Angiotensin Receptors by Cytokines
- 1 July 1997
- journal article
- research article
- Published by Wolters Kluwer Health in Hypertension
- Vol. 30 (1), 35-41
- https://doi.org/10.1161/01.hyp.30.1.35
Abstract
Abstract Although various cytokines are known to be expressed in atherosclerotic lesions, it is not known how these cytokines affect receptors for the peptide hormone angiotensin II (Ang II). We therefore examined the effects of interleukin-1α (220 U/mL [10 ng/mL]), tumor necrosis factor-α (280 U/mL [100 ng/mL]), and interferon gamma (100 U/mL) on Ang II type 1 (AT 1 ) receptors expressed in rat vascular smooth muscle cells. Treatment with interleukin-1α caused a 1.4- to 1.7-fold increase in AT 1 binding after 24 hours ( P <.01) and a 2.3-fold increase in AT 1 mRNA ( P <.05). Tumor necrosis factor-α and interferon gamma did not cause a significant change in AT 1 binding when administered alone but caused a 30% reduction in binding when administered together ( P <.05). The maximal decrease in AT 1 binding (60%, P <.01) was seen with the combination of interleukin-1α with tumor necrosis factor-α and interferon gamma. Although the upregulation of AT 1 by interleukin-1α was unaffected by pretreatment of cells with N -monomethyl- l -arginine or indomethacin, downregulation of AT 1 by interleukin-1α combined with tumor necrosis factor-α/interferon gamma was inhibited by N -monomethyl- l -arginine ( P <.01). Interleukin-1α treatment enhanced Ang II–induced [ 3 H]uridine incorporation, whereas treatment with interleukin-1α combined with tumor necrosis factor-α/interferon gamma attenuated Ang II–induced [ 3 H]uridine and [ 3 H]leucine incorporation. These results demonstrate that interleukin-1α upregulates AT 1 receptors and enhances Ang II–stimulated hypertrophic responses. However, a combination of interleukin-1α with tumor necrosis factor-α and interferon gamma downregulates AT 1 receptors by a nitric oxide–dependent mechanism and reduces Ang II–stimulated trophic responses in vascular smooth muscle cells.Keywords
This publication has 21 references indexed in Scilit:
- Nitric oxide regulates angiotensin II receptors in vascular smooth muscle cellsEuropean Journal of Pharmacology: Molecular Pharmacology, 1995
- Glucocorticoid increases angiotensin II type 1 receptor and its gene expression.Hypertension, 1994
- The pathogenesis of atherosclerosis: a perspective for the 1990sNature, 1993
- Interleukin-1 and the mesangial cellKidney International, 1992
- Identification of two subtypes in the rat type I angiotensin II receptorFEBS Letters, 1992
- Potentiation of inositol trisphosphate production by dexamethasone.Hypertension, 1992
- Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism.Hypertension, 1991
- Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cellsJournal Of Hypertension, 1991
- Detection and localization of tumor necrosis factor in human atheromaThe American Journal of Cardiology, 1990
- Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids.JCI Insight, 1988