Cytokines and vascular reactivity in resistance arteries

2005 ◽  
Vol 288 (3) ◽  
pp. H1016-H1021 ◽  
Author(s):  
Elisabet Vila ◽  
Mercedes Salaices
Keyword(s):  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Vasoactive Mediators ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Small Resistance ◽  
Vascular Beds

Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-α, IL-1β, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and atherogenesis and reinforce the link between inflammation and vascular disease.

scholarly journals Polarized Proteins in Endothelium and Their Contribution to Function

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.

Resistance artery vasodilation to magnesium sulfate during pregnancy and the postpartum state

2005 ◽  
Vol 288 (4) ◽  
pp. H1521-H1525 ◽  
Author(s):  
Anna G. Euser ◽  
Marilyn J. Cipolla
Keyword(s):  
Magnesium Sulfate ◽  
Systemic Blood Pressure ◽  
Mesenteric Arteries ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Buffer Solution ◽  
Sprague Dawley Rats ◽  
Small Resistance ◽  
Vascular Beds ◽  
Hepes Buffer Solution

This study compared the vasodilatory responses to magnesium sulfate (MgSO4) of cerebral and mesenteric resistance arteries and determined whether the responses varied between different gestational groups. Third-order branches (<200 μm) of the posterior cerebral (PCA) and mesenteric arteries (MA) were dissected from nonpregnant (NP; n = 6), late pregnant (LP; day 19, n = 6), and postpartum (PP; day 3, n = 6) Sprague-Dawley rats. A concentration-response curve was performed by replacing the low-MgSO4 (1.2 mM) HEPES buffer solution with increasing concentrations of MgSO4 (4, 6, 8, 16, and 32 mM) and measuring lumen diameter at each concentration. All groups exhibited concentration-dependent dilation to MgSO4, decreasing the amount of tone in the vessels. However, MA were significantly more sensitive to MgSO4 than PCA. Whereas there was no difference in the response between different gestational groups in MA, the PCA from the LP and PP groups showed a significantly diminished response to MgSO4. The percent dilation at 32 mM MgSO4 for PCA versus MA in NP, LP, and PP animals was 36 ± 2 vs. 51 ± 7% ( P < 0.05), 19 ± 9 vs. 54 ± 6% ( P < 0.01 vs. PCA and NP), and 12 ± 5 vs. 52 ± 11% ( P < 0.01 vs. PCA and NP). These results demonstrate that MgSO4 is a vasodilator of small resistance arteries in the cerebral and mesenteric vascular beds. The refractory responses of the PCA in LP and PP groups demonstrate changes in the cerebrovascular vasodilatory mechanisms with gestation. The greater sensitivity of the MA to MgSO4-induced vasodilation suggests that the prophylactic effect of MgSO4 on eclamptic seizures may be more closely related to the lowering of systemic blood pressure than to an effect on cerebral blood flow.

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Hypertension ◽  
2022 ◽  
Author(s):  
Stephane Laurent ◽  
Claudia Agabiti-Rosei ◽  
Rosa Maria Bruno ◽  
Damiano Rizzoni
Keyword(s):  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Vicious Circle ◽  
Large Artery ◽  
Resistance Arteries ◽  
Cross Link ◽  
Small Artery ◽  
Structural Abnormalities ◽  
Small Resistance

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

ABSORPTION SPECTROSCOPY FOR THE ASSESSMENT OF SMALL-ARTERY STRUCTURE

2001 ◽  
Vol 13 (04) ◽  
pp. 175-180
Author(s):  
A. KAUR ◽  
H. FISH ◽  
H. THURSTON ◽  
P. R. SMITH
Keyword(s):  
Blood Vessels ◽  
Transmission Spectra ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Spectroscopic Examination ◽  
Normal Rat ◽  
Small Resistance ◽  
Quasi Newton ◽  
First Time

The assessment of vascular structure gives important information on pathological processes, particularly for the investigation of diseased vessels. In this study the Mulvany wire myogarph is adapted for spectroscopic examination of small arterial blood vessels obtained from hypertensive and normal rat specimens. An experimental study of 20 vessels obtained from adult Wistar rats and Goldblatt (one kidney one clip) hypertensive rats was carried out. Segments of small resistance arteries mounted under isometric conditions on a wire myograph and set to normalised conditions of passive force directly obtained from its circumferential length-tension relationship were morphologically examined and transmission spectra obtained. Features of the observed transmission spectra were extracted by means of an empirical non-linear model using the quasi-Newton method. These features were correlated for the first time with standard descriptors of vessel morplzology, media:lumen ratio and with arterial blood pressure. The extent and significance of such correlations are sufficient to distinguish the presence of hypertension in isolated arterial segments from hypertensive animals. This technique may provide an alternative to light microscopy as well as a potential new tool for the analysis of small blood vessels in the study of vascular disease.

Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats

2001 ◽  
Vol 90 (5) ◽  
pp. 2007-2013 ◽  
Author(s):  
Ziad Tahawi ◽  
Natalia Orolinova ◽  
Irving G. Joshua ◽  
Michael Bader ◽  
Eugene C. Fletcher
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Separate Experiment ◽  
Systemic Hypertension ◽  
Endothelin 1 ◽  
Arterial Blood ◽  
And Control ◽  
Baseline Diameter

Recurrent episodic hypoxia (EH) is a feature of sleep apnea that may be responsible for some chronic cardiovascular sequelae such as systemic hypertension. Chronic EH (8 h/day for 35 days) causes elevation of diurnal resting (unstimulated) mean arterial blood pressure (MAP) in the rat. We used in vivo video microscopy to examine arteriolar reactivity in the cremaster muscle of male Sprague-Dawley rats subjected to 35 days of EH. Cremaster muscles of EH ( n= 6) and control ( n = 6) rats were exposed to varying doses of norepinephrine (NE) (10−10 to 10−5M), ACh (10−9 to 10−5 M), and endothelin-1 (10−12 to 10−8 M). In a separate experiment, EH ( n = 5) and control ( n = 6) rats were given one dose of a nitric oxide synthase (NOS) inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 10−5 M). We also examined endothelial NOS mRNA from the kidneys of EH-stimulated and control (unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHg increase in MAP over 35 days, whereas control rats showed no change. The response to NE and endothelin-1 were similar for EH and control rats. ACh vasodilatation of arterioles in EH rats was significantly attenuated compared with that of controls. The degree of vasoconstriction in response to blockade of the nitric oxide system byl-NAME was significantly less (83% of baseline diameter with l-NAME) for arterioles of EH rats compared with that for controls (61% of baseline diameter), implying lower basal resting nitric oxide release in the EH rats. Whole kidney mRNA endothelial NOS levels were not different between groups. These data support the hypothesis that chronic elevation of blood pressure associated with EH involves increased peripheral resistance from decreased basal release or production of nitric oxide after 35 days of EH.

ET-3 is extracted by and induces potent vasoconstriction in human splanchnic and renal vasculatures

1995 ◽  
Vol 79 (4) ◽  
pp. 1255-1259 ◽  
Author(s):  
E. Weitzberg ◽  
A. Hemsen ◽  
J. M. Lundberg ◽  
G. Ahlborg
Keyword(s):  
Receptor Activation ◽  
Vascular Effects ◽  
Renal Vasoconstriction ◽  
Blood Flows ◽  
Arterial Blood ◽  
Etb Receptor ◽  
Vascular Beds ◽  
Arterial Plasma ◽  
Endothelin 3 ◽  
Renal Vascular

To investigate splanchnic and renal vascular effects and elimination of endothelin-3 (ET-3), ET-3 (10 pmol.kg-1.min-1 iv for 20 min) was given to six healthy male volunteers. Arterial plasma ET-3-like immunoreactivity (ET-3-Li) increased 10-fold to 111 +/- 31 pmol/l (P < 0.01). The initial half-life of plasma ET-3-Li determined in three subjects was 1.7 +/- 0.2 min. The fractional extraction of ET-3-Li was 68 +/- 7% in the splanchnic and 63 +/- 4% in the renal vascular beds. Mean arterial blood pressure fell from 86 +/- 4 to 94 +/- 4 mmHg (10%) (P < 0.05). Splanchnic and renal blood flows fell by 43 +/- 3% (P < 0.05) and 29 +/- 4% (P < 0.05), respectively, during the infusion. Splanchnic and renal vascular resistances rose by 92 +/- 22% (P < 0.05) and 58 +/- 7% (P < 0.05). In conclusion, ET-3 infusion in humans induces splanchnic and renal vasoconstriction of similar magnitude as previously shown during endothelin-1 infusion, presumably by ETB receptor activation. Plasma ET-3 is efficiently extracted in the splanchnic and renal vascular regions.

Effect of a left atrium-pulmonary vein baroreflex on peripheral vascular beds

1977 ◽  
Vol 233 (5) ◽  
pp. H587-H591 ◽  
Author(s):  
T. C. Lloyd ◽  
J. J. Fried
Keyword(s):  
Left Atrial ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Radioactive Microspheres ◽  
Peripheral Vascular ◽  
Blood Flows ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Response Peak ◽  
Vascular Beds

A step increase of left atrial and pulmonary venous pressure from 0 to 25 mmHg was used in anesthetized dogs with controlled arterial blood pressure to generate reflex systemic vasodilation. The resultant response of total peripheral resistance was an initial transient fall of about 40% which spontaneously regressed while the stimulus was maintained. Injections of differently tagged radioactive microspheres were used to measure selected organ blood flows prior to raising atrial pressure, at the response peak, during the steady state, and after recovery. Resistances of skin, skeletal muscle, kidney, and large intestine significantly fell upon atriovenous distention. The response in muscle, which greatly exceeded that of the other organs, was not sustained, whereas resistances of other responding beds remained depressed until the stimulus was removed. No significant responses occurred in small intestine, liver (hepatic artery), or adrenal gland.

Increased superoxide production and altered nitric oxide-mediated relaxation in the aorta of young but not old male relaxin-deficient mice

2015 ◽  
Vol 309 (2) ◽  
pp. H285-H296 ◽  
Author(s):  
Hooi H. Ng ◽  
Maria Jelinic ◽  
Laura J. Parry ◽  
Chen-Huei Leo
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Superoxide Production ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
Small Resistance ◽  
Ros Scavenger ◽  
Relaxation Responses ◽  
Endothelial Nitric Oxide

The vascular effects of exogenous relaxin (Rln) treatment are well established and include decreased myogenic reactivity and enhanced relaxation responses to vasodilators in small resistance arteries. These vascular responses are reduced in older animals, suggesting that Rln is less effective in mediating arterial function with aging. The present study investigated the role of endogenous Rln in the aorta and the possibility that vascular dysfunction occurs more rapidly with aging in Rln-deficient ( Rln−/−) mice. We compared vascular function and underlying vasodilatory pathways in the aorta of male wild-type ( Rln+/+) and Rln−/− mice at 4 and 16 mo of age using wire myography. Superoxide production, but not nitrotyrosine or NADPH oxidase expression, was significantly increased in the aorta of young Rln−/− mice, whereas endothelial nitric oxide (NO) synthase and basal NO availability were both significantly decreased compared with Rln+/+ mice. In the presence of the cyclooxygenase inhibitor indomethacin, sensitivity to ACh was significantly decreased in young Rln−/− mice, demonstrating altered NO-mediated relaxation that was normalized in the presence of a membrane-permeable SOD or ROS scavenger. These vascular phenotypes were not exacerbated in old Rln−/− mice and, in most cases, did not differ significantly from old Rln+/+ mice. Despite the vascular phenotypes in Rln−/− mice, endothelium-dependent and -independent vasodilation were not adversely affected. Our data show a role for endogenous Rln in reducing superoxide production and maintaining NO availability in the aorta but also demonstrate that Rln deficiency does not compromise vascular function in this artery or exacerbate endothelial dysfunction associated with aging.

Morphological and functional alterations of mesenteric small resistance arteries in early renal hypertension in rats

1991 ◽  
Vol 261 (4) ◽  
pp. H1171-H1177 ◽  
Author(s):  
L. Y. Deng ◽  
E. L. Schiffrin
Keyword(s):  
Blood Vessels ◽  
Vascular Reactivity ◽  
Rapid Development ◽  
Renal Hypertension ◽  
Lumen Diameter ◽  
External Diameter ◽  
Effective Pressure ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Small Resistance

We investigated the structure and reactivity of small resistance arteries of two-kidney, one-clip (2K,1C) and one-kidney, one-clip (1K,1C) Goldblatt hypertensive rats within 4-6 wk of development of hypertension. Blood vessels from the mesenteric vascular bed with lumen diameter less than 300 microns were mounted on a wire myograph. The media of the vessel wall was significantly increased and lumen diameter was decreased in 2K,1C and 1K,1C rats. External diameter of blood vessels was reduced in both 2K,1C and 1K,1C rats, whereas cross-sectional area of the wall was increased significantly in 1K,1C rats. Wall tension in response to KCl was significantly lower in 2K,1C and 1K,1C hypertensive rats, whereas tension in response to norepinephrine (NE) was reduced in 1K,1C hypertensive rats but was similar in 2K,1C rats and controls. Active tension in response to arginine vasopressin (AVP) was similar in all groups. As a consequence of the reduced lumen circumference of small arteries, effective pressure in response to NE was similar in hypertensive and control rats, whereas effective pressure in response to AVP was exaggerated in the hypertensive rats. The sensitivity to NE and AVP was similar in all groups. These results show the rapid development of functional and structural changes in small resistance arteries in renal hypertensive rats within 4-6 wk of hypertension, with significant reduction in external and lumen diameters, increased media width, and increased media-to-lumen ratio, which enhance vascular reactivity to vasoconstrictors, in particular NE and AVP.

Abstract MP08: Syndecan-1 is Involved in Osteoprotegerin-induced Vascular Dysfunction

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Augusto C Montezano ◽  
Karla B Neves ◽  
Rheure A Lopes ◽  
Susan Leckerman ◽  
Anastasiya Strembitska ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Vascular Reactivity ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Rho Kinase ◽  
Nitric Oxide Donor ◽  
H2o2 Production ◽  
Resistance Arteries ◽  
Vascular Effects

Osteoprotegerin (OPG), an inhibitor of vascular calcification, has pleiotropic vascular effects independently of its actions on calcification. OPG has been associated with vascular inflammation and remodelling and may be important in cardiovascular disease where OPG levels may be elevated. Molecular mechanisms and functional consequences of OPG stimulation in the vasculature are unclear. We propose that syndecan-1, a membrane glycoprotein, may be important and that reactive oxygen species (ROS) play a role in OPG signalling. Vascular reactivity of resistance arteries from WKY rats was studied by wire myography in the presence or absence of OPG (50 ng/mL) and/or synstatin (SSNT - 10-6M - syndecan-1 inhibitor). Rat endothelial cells (EC) and vascular smooth muscle cells (VSMC) were studied. Levels of ROS were measured by chemiluminescence, Amplex Red (H2O2) and ELISA (nitrotyrosine; peroxynitrite - ONOO-). Protein oxidation and levels were measured by immunoblotting. Exposure of resistance arteries to OPG induced endothelial (decreased relaxation to acetylcholine) and VSMC (decreased relaxation to sodium nitroprusside - SNP) dysfunction, as well as, increased contraction to phenylephrine. All responses were blocked by SSNT, N-acetylcisteine (antioxidant) and ML171 (Nox inhibitor). In EC, OPG-induced ROS production (240±46.1% increase vs. veh, p<0.05) was blocked by SSNT. OPG decreased H2O2 production/release (61±5.4% vs. veh) and increased eNOS Thr 495 phosphorylation (inhibitory site) (100±24% vs. veh, p<0.05). In VSMC, OPG increased H2O2 (69±3%) and ONOO- (43±12%) levels, protein oxidation (61±15%), Rho kinase (200±39%) and myosin light chain activation (55±3%) (all vs. veh, p<0.05). Increase in OPG-induced ONOO- levels was exacerbated by SNP (130±16% vs. veh, p<0.05), a nitric oxide donor. In conclusion, vascular dysfunction elicited by OPG is mediated by syndecan-1 and ROS. Whether syndecan-1 also impacts on OPG-sensitive calcification is unclear. Our data identify a novel molecular mechanism through syndecan- 1/ROS that may underlie injurious effects of OPG.

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