Nitric oxide attenuates the expression of natriuretic peptide receptor C and associated adenylyl cyclase signaling in aortic vascular smooth muscle cells: role of MAPK

2009 ◽  
Vol 296 (6) ◽  
pp. H1859-H1867 ◽  
Author(s):  
Maria Arejian ◽  
Yuan Li ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor

We have earlier shown that the treatment of A10 vascular smooth muscle cells with S-nitroso- N-acetyl-penicillamine (SNAP); nitric oxide donor (NO) for 24 h decreased the expression of natriuretic peptide receptor C (NPR-C) and adenylyl cyclase signaling. The present study was undertaken to examine the implication of different signaling mechanisms in a NO-induced response. The treatment of A10 vascular smooth muscle cells with SNAP decreased the expression of NPR-C and Giα proteins in a time-dependent manner. The expression of Giα proteins was decreased at 6 h, whereas the expression of NPR-C was attenuated at 2 h. The NPR-C-mediated inhibition of adenylyl cyclase was attenuated (∼50%) after 2 h of treatment and was completely abolished after 6 h of treatment. The decreased expression of NPR-C and NPR-C-mediated attenuation of adenylyl cyclase after 2 h of treatment was reversed to control levels by PD-98059, a MEK inhibitor. SNAP also modulated the ERK1/2 phosphorylation in a time-dependent manner; an increase was observed up to 2 h, and, thereafter, the ERK1/2 phosphorylation was decreased. On the other hand, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823 inhibitor of soluble guanylyl cyclase and protein kinase G, respectively, and Mn(III)tetrakis(4-benzoic acid)porphyrin, a scavenger of peroxynitrite, were unable to restore the SNAP-induced decreased expression of NPR-C protein and increased ERK1/2 phosphorylation to control levels. However, the decreased levels of phosphorylated ERK1/2 and Giα proteins were restored to control levels by 8-bromo-cAMP. These results indicate that a temporal relationship follows between a NO-induced decreased expression of NPR-C and Giα proteins. The decreased expression of NPR-C is mediated through cGMP-independent but MAPK-dependent pathway, whereas NO-induced decreased levels of cAMP may contribute to the decreased activation of MAPK and thereby decreased the expression of Giα proteins.

Peroxynitrite inhibits the expression of Giα protein and adenylyl cyclase signaling in vascular smooth muscle cells

2008 ◽  
Vol 294 (2) ◽  
pp. H775-H784 ◽  
Author(s):  
Marcel Bassil ◽  
Yuan Li ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
P38 Map Kinase ◽  
Nitric Oxide Donor ◽  
Dependent Manner

We previously showed that S-nitroso- N-acetylpenicillamine, a nitric oxide donor, decreased the levels and functions of Giα proteins by formation of peroxynitrite (ONOO−) in vascular smooth muscle cells (VSMC). The present studies were undertaken to investigate whether ONOO− can modulate the expression of Giα protein and associated adenylyl cyclase signaling in VSMC. Treatment of A-10 and aortic VSMC with ONOO− for 24 h decreased the expression of Giα-2 and Giα-3, but not Gsα, protein in a concentration-dependent manner; expression was restored toward control levels by 111Mn-tetralis(benzoic acid porphyrin) and uric acid, but not by 1 H[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one (ODQ) and KT-5823. cGMP levels were increased by ∼50% and 150% by 0.1 and 0.5 mM ONOO−, respectively, and attenuated toward control levels by ODQ. In addition, 0.5 mM ONOO− attenuated the inhibition of adenylyl cyclase by ANG II and C-type atrial natriuretic peptide (C-ANP4–23), as well as the inhibition of forskolin-stimulated adenylyl cyclase activity by GTPγS, whereas, the Gs-mediated stimulations were augmented. In addition, 0.5 mM ONOO− decreased phosphorylation of ERK1/2 and p38 MAP kinase and enhanced JNK phosphorylation but did not affect AKT1/3 phosphorylation. These results suggest that ONOO− decreased the expression of Gi proteins and associated functions in VSMC through a cGMP-independent mechanism and may involve the MAP kinase signaling pathway.

Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells

2003 ◽  
Vol 284 (3) ◽  
pp. C674-C680 ◽  
Author(s):  
Jing Zhang ◽  
Peter K. Lauf ◽  
Norma C. Adragna
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Time Dependent ◽  
Platelet Derived Growth Factor ◽  
Dependent Manner

Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner

1991 ◽  
Vol 260 (5) ◽  
pp. H1713-H1717 ◽  
Author(s):  
U. Ikeda ◽  
M. Ikeda ◽  
T. Oohara ◽  
A. Oguchi ◽  
T. Kamitani ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Interleukin 6 ◽  
Thymidine Incorporation ◽  
Tritiated Thymidine ◽  
Muscle Cells ◽  
Thymidine Uptake ◽  
Dependent Manner

We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated “quiescent” VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.

Hypoxia-induced expression of VEGF is reversible in myocardial vascular smooth muscle cells

1997 ◽  
Vol 273 (2) ◽  
pp. H628-H633 ◽  
Author(s):  
J. W. Gu ◽  
T. H. Adair
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Conditioned Media ◽  
Dependent Manner ◽  
Induced Expression ◽  
Protein Levels

We determined whether hypoxia-induced expression of vascular endothelial growth factor (VEGF) can be reversed by a normoxic environment. Dog myocardial vascular smooth muscle cells (MVSMCs) were exposed to hypoxia (1% O2) for 24 h and then returned to normoxia (20% O2). VEGF protein levels increased by more than fivefold after 24 h of hypoxia and returned to baseline within 24 h of the return of the cells to normoxia. Northern blot analysis showed that hypoxia caused a 5.5-fold increase in VEGF mRNA, and, again, the expression was reversed after reinstitution of normoxia. Additional measurements showed that basic fibroblast growth factor and platelet-derived growth factor protein levels were not induced by hypoxia and that hypoxia caused a fourfold decrease in transforming growth factor-beta 1 protein levels. Hypoxia conditioned media from MVSMCs caused human umbilical vein endothelial cells to increase [3H]thymidine incorporation by twofold, an effect that was blocked in a dose-dependent manner by anti-human VEGF antibody. The hypoxia conditioned media had no effect on MVSMC proliferation. These findings suggest that VEGF expression can be bidirectionally controlled by tissue oxygenation, and thus support the hypothesis that VEGF is a physiological regulator of angiogenesis.

scholarly journals Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells

2011 ◽  
Vol 91 (4) ◽  
pp. 694-702 ◽  
Author(s):  
Carl P. Nelson ◽  
Richard D. Rainbow ◽  
Jennifer L. Brignell ◽  
Matthew D. Perry ◽  
Jonathon M. Willets ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
K Channel ◽  
Principal Role ◽  
Channel Regulation
Sign in / Sign up

Export Citation Format

Share Document