Functional effects of visfatin in isolated rat mesenteric small resistance arteries

Background: Obesity is a major cardiovascular risk factor which dramatically impairs endothelium- dependent vasodilation and leads to hypertension and vascular damage. The impairment of the vasomotor response to extracellular autacoids, e.g., acetylcholine, mainly depends on the reduced Nitric Oxide (NO) bioavailability, which hampers vasorelaxation in large conduit arteries. In addition, obesity may affect Endothelium-Dependent Hyperpolarization (EDH), which drives vasorelaxation in small resistance arteries and arterioles. Of note, endothelial Ca2+ signals drive NO release and trigger EDH. Methods: A structured search of bibliographic databases was carried out to retrieve the most influential, recent articles on the impairment of vasorelaxation in animal models of obesity, including obese Zucker rats, and on the remodeling of the endothelial Ca2+ toolkit under conditions that mimic obesity. Furthermore, we searched for articles discussing how dietary manipulation could be exploited to rescue Ca2+-dependent vasodilation. Results: We found evidence that the endothelial Ca2+ could be severely affected by obese vessels. This rearrangement could contribute to endothelial damage and is likely to be involved in the disruption of vasorelaxant mechanisms. However, several Ca2+-permeable channels, including Vanilloid Transient Receptor Potential (TRPV) 1, 3 and 4 could be stimulated by several food components to stimulate vasorelaxation in obese individuals. Conclusion: The endothelial Ca2+ toolkit could be targeted to reduce vascular damage and rescue endothelium- dependent vasodilation in obese vessels. This hypothesis remains, however, to be probed on truly obese endothelial cells.

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Effect of adrenomedullin on the production of endothelin-1 and on its vasoconstrictor action in resistance arteries: evidence for a receptor-specific functional interaction in patients with heart failure

Clinical Science ◽

10.1042/cs1010045 ◽

2001 ◽

Vol 101 (1) ◽

pp. 45-51 ◽

Cited By ~ 3

Author(s):

Chris HILLIER ◽

Mark C. PETRIE ◽

Michael P. LOVE ◽

Fiona JOHNSTON ◽

Margaret R. MACLEAN ◽

...

Keyword(s):

Heart Failure ◽

Hill Coefficient ◽

Receptor Interaction ◽

Resistance Arteries ◽

Functional Interaction ◽

High Potassium ◽

Endothelin 1 ◽

Patients With Heart Failure ◽

Small Resistance ◽

The Hill

Endothelin-1 (ET-1) and adrenomedullin (ADM) are both produced in the arterial wall, but have opposing biological actions. Evidence from experimental animals suggests a functional interaction between ET-1 and ADM. We have tested this in humans. Small resistance arteries were obtained from gluteal biopsies taken from patients with chronic heart failure (CHF) due to coronary heart disease (CHD), or with CHD and preserved ventricular function. The contractile responses to big ET-1 and to ET-1 in both sets of vessels were studied in the absence (control) and presence of ADM at 20 pmol/l (low ADM) or 200 pmol/l (high ADM), using wire myography. ADM did not affect the conversion of big ET-1 into ET-1 in vessels from patients with either CHD or CHF. Low ADM did not alter the contractile response to ET-1 in vessels from patients with CHF. Low ADM was not tested in vessels from patients with CHD, but high ADM did not affect this response in arteries from these patients. High ADM did, however, significantly reduce the vasoconstrictor effect of ET-1 in vessels from patients with CHF. The maximum response, as a percentage of the response to high potassium, was 199% (S.E.M. 25%) in the control experiments (n = 14), 205% (27%) in the low-ADM (n = 7) studies and 150% (17%) in the high-ADM (n = 6) experiments (P < 0.001). Furthermore, the Hill coefficient increased from 0.57±0.05 in the absence of ADM to 1.16±0.15 in the high-ADM experiments, indicating that ADM at 200 pmol/l specifically antagonized one receptor type in vessels from patients with CHF. We conclude that there is a one-site receptor interaction between ADM and ET-1 that is specific for vessels from patients with CHF. This functional interaction between ADM and ET-1 in resistance arteries may be of pathophysiological importance in CHF.

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Effect of a novel stobadine derivative on isolated rat arteries

Interdisciplinary Toxicology ◽

10.2478/intox-2013-0011 ◽

2013 ◽

Vol 6 (2) ◽

pp. 63-66 ◽

Cited By ~ 1

Author(s):

Zuzana Broskova ◽

Ruzena Sotnikova ◽

Jana Nedelcevova ◽

Zsolt Bagi

Keyword(s):

Reactive Oxygen Species ◽

Ex Vivo ◽

Vascular Wall ◽

Scavenging Activity ◽

Oxygen Species ◽

Resistance Arteries ◽

High Potassium ◽

Structural Modifications ◽

Isolated Rat ◽

Coronary Arterioles

Abstract The antioxidant and reactive-oxygen-species-scavenging activity of stobadine has been demonstrated in previous studies. Recently, chemical modification of this leading structure led to the synthesis of other pyridoindole derivatives with significantly increased intrinsic antioxidant efficacy. Further structural modifications of stobadine provided the opportunity to increase bioavailability and attenuate unwanted side effects, such as α-adrenolytic activity. The aim of the work was to evaluate the direct effect of a novel pyridoindole, SMe1EC2, on the vascular wall ex vivo. The vasomotor effect of SMe1EC2 (1×10-8-1×10-4 mol/l) was measured on isolated and pressurized rat cerebral and coronary arterioles using video-microscopy. The effect of SMe1EC2 (1×10-6 and 1×10-5 mol/l) on high potassium-, phenylephrine- or serotonin-induced contraction or acetylcholine-induced relaxation was also determined in aortic rings. We found that SMe1EC2 (1×10-8-1×10-4 mol/l) elicited significant dilatations in both cerebral and coronary arterioles (max dilatation: 25±8% and 18±5% respectively). Yet, SMe1EC2 (1×10-6 and 1×10-5 mol/l) did not influence the tone of aortic rings nor did it affect high potassium-, phenylephrine- or serotonin -induced contractions and acetylcholine-induced relaxation. Thus SMe1EC2 was able to dilate resistance arteries but did not affect aortic contractility. It is likely that SMe1EC2 does not possess α1-adrenolytic and anti-serotoninergic activity in the vascular wall.

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Polarized Proteins in Endothelium and Their Contribution to Function

Journal of Vascular Research ◽

10.1159/000512618 ◽

2021 ◽

pp. 1-27

Author(s):

Abigail G. Wolpe ◽

Claire A. Ruddiman ◽

Phillip J. Hall ◽

Brant E. Isakson

Keyword(s):

Endothelial Cells ◽

Endothelial Function ◽

Planar Cell Polarity ◽

Protein Localization ◽

Peripheral Resistance ◽

Specific Protein ◽

Resistance Arteries ◽

Extracellular Stimuli ◽

Small Resistance ◽

Signaling Domains

Protein localization in endothelial cells is tightly regulated to create distinct signaling domains within their tight spatial restrictions including luminal membranes, abluminal membranes, and interendothelial junctions, as well as caveolae and calcium signaling domains. Protein localization in endothelial cells is also determined in part by the vascular bed, with differences between arteries and veins and between large and small arteries. Specific protein polarity and localization is essential for endothelial cells in responding to various extracellular stimuli. In this review, we examine protein localization in the endothelium of resistance arteries, with occasional references to other vessels for contrast, and how that polarization contributes to endothelial function and ultimately whole organism physiology. We highlight the protein localization on the luminal surface, discussing important physiological receptors and the glycocalyx. The protein polarization to the abluminal membrane is especially unique in small resistance arteries with the presence of the myoendothelial junction, a signaling microdomain that regulates vasodilation, feedback to smooth muscle cells, and ultimately total peripheral resistance. We also discuss the interendothelial junction, where tight junctions, adherens junctions, and gap junctions all convene and regulate endothelial function. Finally, we address planar cell polarity, or axial polarity, and how this is regulated by mechanosensory signals like blood flow.

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Inhibition of hypoxic pulmonary vasoconstriction in isolated rat resistance arteries by atrial natriuretic peptide

CrossRef Listing of Deleted DOIs ◽

10.1183/09031936.97.10092061 ◽

1997 ◽

Vol 10 (9) ◽

pp. 2061-2065 ◽

Cited By ~ 6

Author(s):

T.K. Rogers ◽

J.S. Thompson ◽

A.H. Morice

Keyword(s):

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Hypoxic Pulmonary Vasoconstriction ◽

Resistance Arteries ◽

Pulmonary Vasoconstriction ◽

Isolated Rat ◽

Atrial Natriuretic

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Abstract P287: Endothelial Dysfunction in Small Resistance Arteries of Patients with Severe Obesity: Role of Arginase

Hypertension ◽

10.1161/hyp.68.suppl_1.p287 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Agostino Virdis ◽

Emiliano Duranti ◽

Monica Nannipieri ◽

Marco Anselmino ◽

Andrea Grazi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Severe Obesity ◽

Subcutaneous Tissue ◽

Age Groups ◽

Inhibitory Effect ◽

Resistance Arteries ◽

Small Arteries ◽

Laparoscopic Surgical Procedure ◽

Small Resistance

Nitric oxide (NO) is produced by endothelial NO synthase (eNOS) using the aminoacid L-Arginine. Arginase (Arg) also uses L-Arginine as substrate, converting it in L-Ornitine and urea. An increased Arg activity causes a progressive L-Arginine depletion, which in turn determines a lower NO bioavailability. Studies in murine models of obesity identify Arg as a determinant of endothelial dysfunction. In this study, we evaluated whether Arg might play a role in determining the lower bioavailability of NO in small resistance arteries isolated from subcutaneous tissue of patients with severe obesity (Ob), split in age groups (younger than 30 aa, range 21-29, n=5; older than 30 aa, range 35-56, n=5) vs normoweight controls (Ctrl younger 30 years, range 20-29, n=5; older than 30 yrs, range 36-58, n=5). Each patient underwent a subcutaneous biopsy during a laparoscopic surgical procedure. Small arteries, isolated from periadvential fat, were evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation (VD) was assessed by acetylcholine (Ach, 0,001-100μM). NO availability was assessed by repeating Ach with L-NAME (100μM). Ach was also infused in the presence of norNOHA (10μM, Arg inhibitor). In Ctrl, VD induced by Ach was inhibited by L-NAME and not modified by norNOHA. Ob younger exhibited a reduced VD induced by Ach vs Ctrl of the same age, a reduced inhibition by L-NAME, and a potentiating effect by norNOHA, which also normalized the inhibitory effect of L-NAME on Ach. In Ob older, VD induced by Ach was reduced vs Ob younger, resistant to L-NAME and not modified by norNOHA. In conclusions, in small arteries from younger Ob, the Arg inhibition improves endothelial function by increasing the NO availability, while in older Ob Arg does not seem to play any role in endothelial dysfunction.

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Pharmacology of vasodilators

ESC CardioMed ◽

10.1093/med/9780198784906.003.0034 ◽

2018 ◽

pp. 180-184

Author(s):

Stéphane Laurent

Keyword(s):

Enzyme Inhibitors ◽

Angiotensin Receptor Blockers ◽

Angiotensin Converting Enzyme Inhibitors ◽

Organic Nitrates ◽

Channel Blockers ◽

Resistance Arteries ◽

Converting Enzyme Inhibitors ◽

Receptor Blockers ◽

Small Resistance ◽

Direct Acting

Antihypertensive and antianginal agents are differentially able to vasodilate small resistance arteries, large conducting arteries, and epicardial coronary arteries. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and alpha-adrenergic antagonists are not addressed here, since they are discussed in specific chapters. This chapter discusses the pharmacology of calcium channel blockers, nitrovasodilators, and direct-acting vasodilators. Dihydropyridines, such as nifedipine and amlodipine, are compared to the non-dihydropyridine agents verapamil and diltiazem. Organic nitrates, such as nitroglycerine and isosorbide dinitrate, are compared to inorganic nitrates, such as sodium nitroprusside. Molsidomine and nicorandil are also discussed. Finally, the pharmacology of direct-acting vasodilators focuses on minoxidil and hydralazine. Pharmacology of mechanisms of action is detailed to better understand therapeutic indications and side effects.

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