Selected Contribution: Cerebrovascular NOS and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-α

2001 ◽  
Vol 91 (5) ◽  
pp. 2391-2399 ◽  
Author(s):  
Greg G. Geary ◽  
Anne Marie McNeill ◽  
Jose A. Ospina ◽  
Diana N. Krause ◽  
Kenneth S. Korach ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Estrogen Treatment ◽  
Wild Type ◽  
Cyclooxygenase 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-α knockout (αERKO) mice were used to test whether estrogen acts via ER-α. Mice were ovariectomized, with or without estrogen replacement, and cerebral blood vessels were isolated 1 mo later. Estrogen increased levels of endothelial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mice but was ineffective in αERKO mice. Endothelium-denuded middle cerebral artery segments from all animals constricted when pressurized. In denuded arteries from αERKO but not wild-type mice, estrogen treatment enhanced constriction. In endothelium-intact, pressurized arteries from wild-type estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethacin were greater in arteries from wild-type estrogen-treated mice compared with arteries from untreated wild-type mice. In contrast, estrogen treatment of αERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-α regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effects of estrogen on cerebral artery reactivity.

Abstract WP103: Endothelial Nitric Oxide Synthase Regulates White Matter Changes after Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xu Cui ◽  
Michael Chopp ◽  
Tao Yan ◽  
Ruizhuo Ning ◽  
Cynthia Roberts ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
White Matter ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Wild Type ◽  
White Matter Damage ◽  
White Matter Changes ◽  
Significant Difference ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Stroke induced white matter damage is associated with neurological functional deficits, but the underlying mechanisms are not well understood. Endothelial nitric oxide synthase knockout (eNOS-/-) mice exhibited a higher mortality, more severe neurological functional deficit, and decreased neurogenesis, angiogenesis and arteriogenesis after stroke than wild type mice. There are no reports as to whether eNOS is related to the white matter change post-stroke. Methods: Adult male C57BL/6 WT and eNOS -/- mice were subjected to permanent middle cerebral artery occlusion (MCAo) by a filament and sacrificed 7 days after MCAo. Functional evaluation, infarct volume measurement, and immunostaining for analysis of white matter changes were performed. Results: There is no significant difference in the infarction volume between wild type and eNOS -/- (wild type : 23.09%±3.32%; eNOS-/-: 27.83%±4.92%, p=0.436, n=9/group). However, eNOS -/- mice showed significantly decreased functional outcome tested by the singal pellet reaching test (wild type: 38.46%%±1.43%, eNOS-/-: 27.45%±2.41%, p=0.0017). eNOS -/- mice also exhibited increased white matter damage compared to wild type mice, including decrease: 1. Axonal density stained by Bielshowsky Silver in the ipsilateral striatal bundles (wild type: 22.06%±3.0%, eNOS-/-: 13.32%±2.18%,, p=0.031), and in the contralateral striatal bundles (wild type: 65.35%±3.97%, eNOS-/-: 29.38%±5.84%, p=0.02); 2. Density of phasphorylated neurofilament by SMI31-immunoflureoscent staining (wild type: 24.11%±2.06%, eNOS-/-: 7.90%±1.70%, p=0.009); 3. The number of CNPase-positive oligodendrocytes in the ischemic border (wild type: 52.23±5.10, eNOS-/-: 35.59±5.33, p=0.041); 4. The number of NG2-positive oligodendrocyte progenitors in the ischemic border (wild type: 26.22±2.31, eNOS-/-: 18.38±1.95, p=0.0187). There is no significant difference in the density of Luxol fast blue stained myelin in the ipsilateral striatal bundles between wild type and eNOS -/- mice (wild type: 25.21%±3.64%; eNOS-/-: 21.39%±6.29%, p=0.260). Conclusions: We are the first to report that eNOS not only regulates vascular changes and neurogenesis, but also plays an important role in white matter changes after stroke.

scholarly journals Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries

1997 ◽  
Vol 94 (23) ◽  
pp. 12568-12573 ◽  
Author(s):  
A. F. Y. Chen ◽  
S.-W. Jiang ◽  
T. B. Crotty ◽  
M. Tsutsui ◽  
L. A. Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Mesenchymal stem cells promote mesenteric vasodilation through hydrogen sulfide and endothelial nitric oxide

2019 ◽  
Vol 317 (4) ◽  
pp. G441-G446 ◽  
Author(s):  
Jan Te Winkel ◽  
Quincy E. John ◽  
Brian D. Hosfield ◽  
Natalie A. Drucker ◽  
Amitava Das ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Wild Type ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Mesenteric ischemia is a devastating process that can result in intestinal necrosis. Mesenchymal stem cells (MSCs) are becoming a promising treatment modality. We hypothesized that 1) MSCs would promote vasodilation of mesenteric arterioles, 2) hydrogen sulfide (H2S) would be a critical paracrine factor of stem cell-mediated vasodilation, 3) mesenteric vasodilation would be impaired in the absence of endothelial nitric oxide synthase (eNOS) within the host tissue, and 4) MSCs would improve the resistin-to-adiponectin ratio in mesenteric vessels. H2S was measured with a specific fluorophore (7-azido-3-methylcoumarin) in intact MSCs and in cells with the H2S-producing enzyme cystathionine β synthase (CBS) knocked down with siRNA. Mechanical responses of isolated second- and third-order mesenteric arteries (MAs) from wild-type and eNOS knockout (eNOSKO) mice were monitored with pressure myography, after which the vessels were snap frozen and later analyzed for resistin and adiponectin via multiplex beaded assay. Addition of MSCs to the myograph bath significantly increased vasodilation of norepinephrine-precontracted MAs. Knockdown of CBS in MSCs decreased H2S production by MSCs and also decreased MSC-initiated MA dilation. MSC-initiated vasodilation was further reduced in eNOSKO vessels. The MA resistin-to-adiponectin ratio was higher in eNOSKO vessels compared with wild-type. These results show that MSC treatment promotes dilation of MAs by an H2S-dependent mechanism. Furthermore, functional eNOS within the host mesenteric bed appears to be essential for maximum stem cell therapeutic benefit, which may be attributable, in part, to modifications in the resistin-to-adiponectin ratio. NEW & NOTEWORTHY Stem cells have been shown to improve survival, mesenteric perfusion, and histological injury scores following intestinal ischemia. These benefits may be due to the paracrine release of hydrogen sulfide. In an ex vivo pressure myography model, we observed that mesenteric arterial dilation improved with stem cell treatment. Hydrogen sulfide release from stem cells and endothelial nitric oxide synthase within the vessels were critical components of optimizing stem cell-mediated mesenteric artery dilation.

scholarly journals Vasodilator mechanisms in the coronary circulation of endothelial nitric oxide synthase-deficient mice

2000 ◽  
Vol 279 (4) ◽  
pp. H1906-H1912 ◽  
Author(s):  
Kathryn G. Lamping ◽  
Daniel W. Nuno ◽  
Edward G. Shesely ◽  
Nobuyo Maeda ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Coronary Arteries ◽  
Endothelial Nitric Oxide Synthase ◽  
Coronary Circulation ◽  
Wild Type ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Endothelium Dependent Relaxation ◽  
Deficient Mice

Previous studies have demonstrated that responses to endothelium-dependent vasodilators are absent in the aortas from mice deficient in expression of endothelial nitric oxide synthase (eNOS −/− mice), whereas responses in the cerebral microcirculation are preserved. We tested the hypothesis that in the absence of eNOS, other vasodilator pathways compensate to preserve endothelium-dependent relaxation in the coronary circulation. Diameters of isolated, pressurized coronary arteries from eNOS −/−, eNOS heterozygous (+/−), and wild-type mice (eNOS +/+ and C57BL/6J) were measured by video microscopy. ACh (an endothelium-dependent agonist) produced vasodilation in wild-type mice. This response was normal in eNOS +/− mice and was largely preserved in eNOS −/− mice. Responses to nitroprusside were also similar in arteries from eNOS +/+, eNOS +/−, and eNOS −/− mice. Dilation to ACh was inhibited by N G-nitro-l-arginine, an inhibitor of NOS in control and eNOS −/− mice. In contrast, trifluoromethylphenylimidazole, an inhibitor of neuronal NOS (nNOS), decreased ACh-induced dilation in arteries from eNOS-deficient mice but had no effect on responses in wild-type mice. Indomethacin, an inhibitor of cyclooxygenase, decreased vasodilation to ACh in eNOS-deficient, but not wild-type, mice. Thus, in the absence of eNOS, dilation of coronary arteries to ACh is preserved by other vasodilator mechanisms.

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

2002 ◽  
Vol 282 (6) ◽  
pp. L1272-L1278 ◽  
Author(s):  
Shari M. Leuwerke ◽  
Aditya K. Kaza ◽  
Curtis G. Tribble ◽  
Irving L. Kron ◽  
Victor E. Laubach
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Compensatory Growth ◽  
Lung Growth ◽  
Wild Type ◽  
Compensatory Lung Growth ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Deficient Mice

Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS−/−), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS−/− mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS−/− mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth.

Sign in / Sign up

Export Citation Format

Share Document