Regulatory interaction of cytoskeleton-associated proteins with soluble guanylyl cyclase in vascular smooth muscle

2018 ◽  
Vol 6 (Suppl. 1) ◽  
pp. A1.3
Author(s):  
Alexander Kollau
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Regulatory Interaction ◽  
Associated Proteins

scholarly journals Modulation of nitric oxide-stimulated soluble guanylyl cyclase activity by cytoskeleton-associated proteins in vascular smooth muscle

2018 ◽  
Vol 156 ◽  
pp. 168-176 ◽  
Author(s):  
Alexander Kollau ◽  
Bernd Gesslbauer ◽  
Michael Russwurm ◽  
Doris Koesling ◽  
Antonius C.F. Gorren ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Cyclase Activity ◽  
Associated Proteins ◽  
Guanylyl Cyclase Activity

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells

1995 ◽  
Vol 269 (2) ◽  
pp. F212-F217 ◽  
Author(s):  
K. S. Lau ◽  
O. Nakashima ◽  
G. R. Aalund ◽  
L. Hogarth ◽  
K. Ujiie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Tnf Alpha ◽  
No Production ◽  
Ifn Gamma ◽  
Oxide Synthase

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

scholarly journals Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

2021 ◽  
Vol 22 (21) ◽  
pp. 11412
Author(s):  
Cheng Zhong ◽  
Minze Xu ◽  
Sengül Boral ◽  
Holger Summer ◽  
Falk-Bach Lichtenberger ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Mrna Expression ◽  
Guanylyl Cyclase ◽  
Pde5 Inhibitor ◽  
Soluble Guanylyl Cyclase ◽  
Mesenteric Arteries ◽  
No Donor ◽  
Diabetic Vasculopathy ◽  
Endothelial Nitric Oxide

Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10−6 mol L−1) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10−6 mol L−1) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.

Hyperpolarization of murine small caliber mesenteric arteries by activation of endothelial proteinase-activated receptor 2

2004 ◽  
Vol 82 (12) ◽  
pp. 1103-1112 ◽  
Author(s):  
John J McGuire ◽  
Morley D Hollenberg ◽  
Brian M Bennett ◽  
Chris R Triggle
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Blood Vessels ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Induced Hypotension ◽  
Protease Activated Receptor 2

Activation of endothelial proteinase-activated receptor 2 (PAR-2) relaxes vascular smooth muscle (VSM) and causes hypotension by nitric oxide (NO)–prostanoid-dependent and -independent mechanisms. We investigated whether endothelium-dependent hyperpolarization of VSM was the mechanism whereby resistance caliber arteries vasodilated independently of NO. VSM membrane potentials and isometric tension were measured concurrently to correlate the electrophysiological and mechanical changes in murine small caliber mesenteric arteries. In uncontracted arteries, the PAR-2 agonist, SLIGRL-NH2 (0.1 to 10 µmol/L), hyperpolarized the VSM membrane potential only in endothelium-intact arterial preparations. This response was unaltered by treatment of arteries with inhibitors of NO synthases (L-NAME), soluble guanylyl cyclase (ODQ), and cyclooxygenases (indomethacin). L-NAME, ODQ, and indomethacin also failed to inhibit SLIGRL-NH2-induced hyperpolarization and of cirazoline-contracted mesenteric arteries. However, in blood vessels that were depolarized and contracted with 30 mmol/L KCl, the effects of the SLIGRL-NH2 on membrane potential and tension were not observed. SLIGRL-NH2-induced hyperpolarization and relaxation was inhibited completely by the combination of apamin plus charybdotoxin, but only partially inhibited after treatment with the combination of barium plus ouabain, suggesting an important role for SKCa and IKCa channels and a lesser role for Kir channels and Na+/K+ ATPases in the hyperpolarization response. We concluded that activation of endothelial PAR-2 hyperpolarized the vascular smooth muscle (VSM) cells of small caliber arteries, without requiring the activation of NO synthases, cyclooxygenases, or soluble guanylyl cyclase. Indeed, this hyperpolarization may be a primary mechanism for PAR-2–induced hypotension in vivo.Key words: proteinase-activated receptor 2, protease-activated receptor 2, endothelium, vascular smooth muscle, hyperpolarization, blood vessels, transgenic mice, vasoactive peptides.

scholarly journals Inhibition of Vascular Smooth Muscle Growth by the Soluble Guanylyl Cyclase Activator BAY 60–2770

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Danielle Nicole Martin ◽  
Shaquria P Adderley ◽  
Chintamani N Joshi ◽  
William Durante ◽  
David A Tulis
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Muscle Growth ◽  
Soluble Guanylyl Cyclase ◽  
Cyclase Activator

scholarly journals Role of Aging Versus the Loss of Estrogens in the Reduction in Vascular Function in Female Rats

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 212-219 ◽  
Author(s):  
James P. Stice ◽  
Jason P. Eiserich ◽  
A. A. Knowlton
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Vascular Function ◽  
Soluble Guanylyl Cyclase ◽  
Female Rats ◽  
Oxide Synthase

Although aging is known to lead to increased vascular stiffness, the role of estrogens in the prevention of age-related changes in the vasculature remains to be elucidated. To address this, we measured vascular function in the thoracic aorta in adult and old ovariectomized (ovx) rats with and without immediate 17β-estradiol (E2) replacement. In addition, aortic mRNA and protein were analyzed for proteins known to be involved in vasorelaxation. Aging in combination with the loss of estrogens led to decreased vasorelaxation in response to acetylcholine and sodium nitroprusside, indicating either smooth muscle dysfunction and/or increased fibrosis. Loss of estrogens led to increased vascular tension in response to phenylephrine, which could be partially restored by E2 replacement. Levels of endothelial nitric oxide synthase and inducible nitric oxide synthase did not differ among the groups, nor did total nitrite plus nitrate levels. Old ovx exhibited decreased expression of both the α and β-subunits of soluble guanylyl cyclase (sGC) and had impaired nitric oxide signaling in the vascular smooth muscle. Immediate E2 replacement in the aged ovx prevented both the impairment in vasorelaxation, and the decreased sGC receptor expression and abnormal sGC signaling within the vascular smooth muscle. The combination of loss of estradiol and aging leads to increased constriction (phenylephrine) and decreased relaxation with nitric oxide. Reduced soluble guanylyl cyclase mediates these changes.

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