scholarly journals Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation

Circulation ◽  
1999 ◽  
Vol 100 (19) ◽  
pp. 1951-1957 ◽  
Author(s):  
Stephen J. Duffy ◽  
Sally F. Castle ◽  
Richard W. Harper ◽  
Ian T. Meredith
Keyword(s):  
Nitric Oxide ◽  
Coronary Circulation ◽  
Flow Mediated Dilation ◽  
Metabolic Vasodilation

Peroxynitrite reduces the endothelium-derived hyperpolarizing factor component of coronary flow-mediated dilation in PECAM-1-knockout mice

2006 ◽  
Vol 290 (1) ◽  
pp. R57-R65 ◽  
Author(s):  
Yanping Liu ◽  
Aaron H. Bubolz ◽  
Yang Shi ◽  
Peter J. Newman ◽  
Debra K. Newman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Coronary Flow ◽  
Cell Adhesion Molecule ◽  
Coronary Circulation ◽  
Flow Mediated Dilation ◽  
Wild Type ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is capable of transducing signals in endothelial cells exposed to shear; however, the biological consequences of this signal transduction are unknown. Because shear stress elicits flow-mediated dilation (FMD), we examined whether steady-state FMD in mouse coronary arteries (MCAs) is affected in the PECAM-1 knockout (KO) mouse. MCAs were isolated from wild-type (WT) or KO mice and prepared for videomicroscopy, histofluorescence, Western blotting, and immunohistochemistry. FMD was examined in the absence and presence of Nω-nitro-l-arginine methyl ester (l-NAME) and l-NAME+indomethacin (INDO). FMD was reduced in KO relative to WT MCAs, but the l-NAME-inhibitable portion of FMD was similar between the two. The INDO-sensitive component of FMD was diminished in KO MCAs. In contrast, the residual component of dilation, presumably because of endothelium-derived hyperpolarizing factor (EDHF), was abolished in KO MCAs. Histofluorescence showed relatively more superoxide (O2−·; oxy-ethidium fluorescence) and peroxide production (dihydrochlorofluorescene fluoresecence) in KO MCAs at rest. Flow augmented O2−· and peroxide production in WT MCAs but had little effect on KO MCAs. Enhanced nitric oxide generation was observed in arteries from KO mice, accompanied with increased eNOS S1177 phosphorylation. In vessels from KO mice, treatment with ebselen decreased peroxynitrite (ONOO−) formation and improved the reduced FMD, largely due to restoration of the presumed EDHF component. These results suggest that PECAM-1 is necessary for normal FMD in the mouse coronary circulation. In the absence of this adhesion and signaling molecule, ONOO− production is increased concomitant with a reduction in both the EDHF and INDO-sensitive components of FMD.

scholarly journals Prostacyclin, but not nitric oxide, mediates the vasodilator response to endothelin-1 in the coronary circulation

1996 ◽  
Vol 27 (2) ◽  
pp. 322
Author(s):  
Jay H. Traverse ◽  
Dianne L. Judd ◽  
Todd J. Pavek ◽  
Melanie J. Crampton ◽  
Robert J. Bache
Keyword(s):  
Nitric Oxide ◽  
Coronary Circulation ◽  
Endothelin 1 ◽  
Vasodilator Response

scholarly journals Is Flow-Mediated Dilation Nitric Oxide Mediated?

Hypertension ◽  
2014 ◽  
Vol 63 (2) ◽  
pp. 376-382 ◽  
Author(s):  
Daniel J. Green ◽  
Ellen A. Dawson ◽  
Hans M.M. Groenewoud ◽  
Helen Jones ◽  
Dick H.J. Thijssen
Keyword(s):  
Nitric Oxide ◽  
Flow Mediated Dilation

Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function

2005 ◽  
Vol 99 (4) ◽  
pp. 1621-1621 ◽  
Author(s):  
Clare E. Austin
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

Abstract 089: CD36 Genetic Variant Impacts Nitric Oxide Regulation of Endothelial Function: Response to Chronic Treatment with Phosphodiesterase 5 Inhibition

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Cyndya A Shibao ◽  
Jorge E Celedonio ◽  
Latisha Gregory-Love ◽  
Claudia E Ramirez ◽  
Amy C Arnold ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Chronic Treatment ◽  
Genetic Variant ◽  
Sildenafil Citrate ◽  
Flow Mediated Dilation ◽  
Fasting Insulin ◽  
The Mean ◽  
Phosphodiesterase 5

CD36, a scavenger receptor expressed on endothelial cells, interacts with thrombospodin-1, a matrix protein that modulates nitric oxide-soluble guanylate cyclase (NO-sGC) signaling. CD36 genetic variants associate with endothelial dysfunction, atherosclerosis, hypertension and insulin resistance. A coding variant of CD36 (rs3211938, G/T genotype) that causes partial CD36 deficiency (50% reduction) is common (~18%) in African Americans (AA); however, it is unknown, if this genotype influences NO-dependent endothelial function. This study examined whether potentiating NO-sGC pathways with the phosphodiesterase 5 inhibitor, sildenafil citrate, improves endothelial function and insulin sensitivity in AA women with or without the G/T genotype. Forty-six AA women with metabolic syndrome (MetS) participated in a 4-week, parallel-arm, double-blind, and placebo-controlled study. Carefully matched subjects were randomly assigned to sildenafil citrate 20 mg TID versus placebo; sildenafil (n= 23, 42±10 years old, BMI 39±5 kg/m2, fasting insulin 15±8 uU/ml) and placebo (n=23, age 43±10, BMI 39±6 kg/m2, fasting insulin 14±10 uU/ml). Primary endpoints were insulin sensitivity and endothelial function measured by intravenous glucose tolerance test and flow mediated dilation, respectively. Treatment compliance was documented with plasma sildenafil levels (mean 57±50 ng/ml). There was no difference in insulin sensitivity (p=0.676) or flow-mediated dilation (p=0.649) between intervention groups. However, subgroup analyses showed a significant interaction between sildenafil citrate treatment and G/T genotype (p=0.018). Sildenafil citrate improved endothelial function in G/T carriers (the mean difference: 2.9, the 95% CI: -0.90 to 6.8, p = 0.126) and decreased endothelial function in T/T carriers (the mean difference: -2.6, the 95% CI: -5.1 to -0.1, p = 0.040). We conclude that the rs3211938 common CD36 genetic variant influences NO-dependent endothelial function in response to chronic treatment with phosphodiesterase 5 inhibition. Further studies are needed to determine if rs3211938 and other common CD36 genotypes influence endothelial function and the inter-individual variability in response to the drug.

Abstract 3628: Neuronal Nitric Oxide Synthase (nNOS) Regulates Basal Flow in the Human Coronary Circulation I n Vivo

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mike Seddon ◽  
Phil Chowienczyk ◽  
Narbeh Melikian ◽  
Rafal Dworakowski ◽  
Barbara Casadei ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Coronary Flow ◽  
Vascular Tone ◽  
Coronary Circulation ◽  
Physiological Regulation ◽  
Intracoronary Doppler ◽  
Basal Flow

Endothelial NO synthase (eNOS) is thought to be the major source of nitric oxide (NO) involved in the local regulation of human vascular tone. However, in studies using a selective neuronal NOS (nNOS) inhibitor S-methyl-L-thiocitrulline (SMTC), we recently reported that basal human forearm blood flow is regulated by nNOS. SMTC had no effect on acetylcholine-induced vasodilatation which however was inhibited by the non-selective NOS inhibitor N G monomethyl-L-arginine (L-NMMA). This study investigated the effects of nNOS in the human coronary circulation in vivo . We studied patients undergoing diagnostic cardiac catheterisation who had angiographically normal coronary arteries. Coronary flow velocity was measured by an intracoronary Doppler wire and epicardial artery diameter by QCA. We compared the effects of intracoronary SMTC or L-NMMA infusion on basal flow and the responses to substance P and isosorbide dinitrate (endothelium-dependent and -independent dilators, respectively). L-NMMA (25 μmol/min) reduced basal coronary flow by 22.3±5.3% and inhibited dilation to substance P (20 pmol/min) by 57±5.7% (n=8; both P<0.01). SMTC (0.625 μmol/min) also reduced basal flow (−34.8±6.3%; n=8; P<0.01), but had no effect on the response to substance P (inhibited by −2±14%; P=NS). The effects of SMTC were abolished by L-arginine (240μmol/ min; n=3). Both L-NMMA and SMTC reduced epicardial artery diameter (−2.5±0.6% and −2.8±0.9% respectively; P<0.05) but only L-NMMA reduced dilatation to substance P (5.6±1.3% before versus 3.0±0.8% after L-NMMA; P<0.05). These data indicate that local nNOS-derived NO regulates basal coronary blood flow in humans in vivo , whereas substance P-stimulated vasodilatation is eNOS-mediated. Our results indicate that nNOS and eNOS have distinct local roles in the physiological regulation of human coronary vascular tone in vivo .

Flow-mediated dilatation revisited

2005 ◽  
Vol 99 (4) ◽  
pp. 1623-1623 ◽  
Author(s):  
Robinson Joannides ◽  
Jeremy Bellien
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
Flow Mediated Dilatation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

Endogenous adenosine modulates alpha 2- but not alpha 1-adrenergic constriction of coronary arterioles

1995 ◽  
Vol 268 (6) ◽  
pp. H2487-H2494 ◽  
Author(s):  
D. V. DeFily ◽  
J. L. Patterson ◽  
W. M. Chilian
Keyword(s):  
Coronary Circulation ◽  
Beta Blockade ◽  
Adenosine Receptor Antagonist ◽  
Endogenous Production ◽  
Adenosine Antagonism ◽  
Metabolic Stimulation ◽  
Metabolic Vasodilation ◽  
Baseline Diameter ◽  
Made In ◽  
Coronary Arterioles

In the coronary circulation alpha-adrenergic constriction competes with metabolic vasodilation. Because adenosine is produced by the working myocardium and metabolic stimulation results in arteriolar dilation, we tested the hypothesis that coronary arteriolar alpha-adrenergic constriction is attenuated by the endogenous production of adenosine. To test this hypothesis, using fluorescence microscopy during stroboscopic epi-illumination of the epicardial microvasculature, we measured the diameter of coronary arterioles in anesthetized open-chest dogs. Measurements were made in the presence of beta-blockade during selective alpha 1- or alpha 2-adrenoceptor activation (phenylephrine or B-HT-933, respectively) before and in the presence of the nonselective adenosine receptor antagonist 8-p-sulfophenyltheophylline (8-pSPT) and expressed as a percent change in microvascular diameter relative to baseline. alpha 1-Activation produced constriction of coronary arterioles under control conditions, which was not augmented after adenosine antagonism (-12 +/- 2 vs. -7 +/- 3%). In contrast, alpha 2-activation did not constrict coronary arterioles under control conditions; however, blockade of adenosine receptors unmasked a significant constriction (0 +/- 2 vs. -7 +/- 2%, P < 0.05). Also adenosine antagonism did not significantly alter the baseline diameter of coronary arterioles. These results demonstrate that endogenously produced adenosine modulates alpha 2-adrenergic constriction of coronary arterioles but not alpha 1-adrenergic constriction, and therefore we speculate that the competition between alpha-adrenergic constriction and metabolic vasodilation is mediated by the alpha 1-adrenoceptor.

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