Intraluminal Pressure Modulates Vascular Contractility of Perfused Mesenteric Resistance Arteries

1992 ◽  
Vol 5 (8) ◽  
pp. 542-547 ◽  
Author(s):  
Michael A Thiel ◽  
Andreas H. Bock ◽  
Fritz R. Bühler ◽  
Thomas F. Lüscher
Keyword(s):  
Intraluminal Pressure ◽  
Resistance Arteries ◽  
Vascular Contractility

Abstract 064: Transactivation of Egfr by Tgfβ Induces Hypertension by Increasing Arteriolar Myogenic Response

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Daniela Carnevale ◽  
Manuel Casaburo ◽  
Stefania Fardella ◽  
Giuseppe Cifelli ◽  
Gualtiero Innocenzi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Egf Receptor ◽  
Intraluminal Pressure ◽  
Classical Type ◽  
Developmental Defect ◽  
Resistance Arteries ◽  
Tgfβ Signaling ◽  
Egfr Transactivation ◽  
Hypertensive Patients ◽  
Egfr Inhibition

Emilin1 (E1) is a protein of the extracellular matrix regulating TGFβ bioavailability through proTGFβ proteolysis. E1 KO mice are hypertensive with increased TGFβ activation. As E1 is expressed in vessels from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of homeostatic role in the adult. To dissect this issue, we used a conditional gene targeting inactivating E1 in smooth muscle cells (SMCs) of adult mice, by the use of E1flox/flox and tamoxifen (TAM) inducible Cre recombinase specific for SMCs. When E1fl/fl mice carrying the Smmhc-CreERT2 were given TAM blood pressure significantly increased (SBP: 123±2 vs basal condition 104±3;***p< 0.001) as well as myogenic tone (MT) of resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg). How increased TGFβ signaling in SMCs could determine an increased MT is still unknown. Relevant to this, we found that the higher TGFβ signaling in E1 KO SMCs stimulates heparin binding epidermal growth factor (HB-EGF) and subsequent transactivation of the EGF receptor, a mechanism typically implied in potentiating MT. When mesenteric resistance arteries from E1 were subjected to step-increases in intraluminal pressure, EGFR inhibition rescued the increased MT. At the molecular level, TGFβ-induced EGFR transactivation resulted into the activation of transient receptor potential classical type 6 (TRPC6) and melastatin type 4 (TRPM4) channels. To put our data into translational perspective, we measured MT of resistance arteries isolated from hypertensive patients and normotensive subjects, finding increased MT (HT 16.4±0.7; NT 11±0.4;***p< 0.001) and TGFβ signaling in the former group. By using a neutralizing anti-TGFβ or an anti-EGFR we found a normalization of the increased MT (HT+anti-TGFβ 11±1.3; NT+anti-TGFβ 11.2±1.2;***p< 0.001 and HT+anti-EGFR 9±0.6; NT+anti-EGFR 10.8±1.1;***p< 0.001), thus confirming the relevance of TGFβ-EGFR pathway in humans. Taken together these data suggest that primary increase of MT induced by TGFβ-EGFR transactivation can cause hypertension and that higher TGFβ signaling and MT are common alterations of resistance arteries of hypertensive patients.

Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats

2002 ◽  
Vol 283 (6) ◽  
pp. H2160-H2168 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Kristopher G. Maier ◽  
David W. Stepp
Keyword(s):  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Oxidant Stress ◽  
Intraluminal Pressure ◽  
Zucker Rats ◽  
Radical Scavengers ◽  
Resistance Arteries ◽  
Obese Zucker Rats ◽  
Cytochrome P 450

This study characterized myogenic activation of skeletal muscle (gracilis) resistance arteries from lean (LZR) and obese Zucker rats (OZR). Arteries from OZR exhibited increased myogenic activation versus LZR; this increase was impaired by endothelium denudation or nitric oxde synthase inhibition. Treatment of vessels with 17-octadecynoic acid impaired responses in both strains by comparable amounts. Dihydroethidine microfluorography indicated elevated vascular superoxide levels in OZR versus LZR; immunohistochemistry demonstrated elevated vascular nitrotyrosine levels in OZR, indicating increased peroxynitrite presence. Vessel treatment with oxidative radical scavengers (polythylene glycol-superoxide dismutase/catalase) or inhibition of Ca2+-activated K+(KCa) channels (iberiotoxin) did not alter myogenic activation in LZR but normalized activation in OZR. Application of peroxynitrite to vessels of OZR caused a greater vasoconstriction versus LZR; the response was impaired in OZR by elevated intraluminal pressure and was abolished in both strains by iberiotoxin. These results suggest that enhanced myogenic activation of gracilis arteries of OZR versus LZR 1) is not due to alterations in cytochrome P-450 contribution, and 2) may be due to elevated peroxynitrite levels inhibiting KCa channels following increased intraluminal pressure.

scholarly journals Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice

2018 ◽  
Vol 314 (5) ◽  
pp. H1022-H1032 ◽  
Author(s):  
Zoe Ashley ◽  
Sama Mugloo ◽  
Fiona J. McDonald ◽  
Martin Fronius
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Nitric Oxide Synthase ◽  
Signaling Pathways ◽  
Endothelial Nitric Oxide Synthase ◽  
Mesenteric Arteries ◽  
Intraluminal Pressure ◽  
Resistance Arteries ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

A potential “new player” in arteries for mediating shear stress responses is the epithelial Na+ channel (ENaC). The contribution of ENaC as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance), is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (third-order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no flow) and in response to increased intraluminal pressure and shear stress using a pressure myograph. These protocols were performed in the absence and presence of the ENaC inhibitor amiloride (10 µM) and after inhibition of endothelial nitric oxide synthase (eNOS) by Nω-nitro-l-arginine methyl ester (l-NAME; 100 µM). Under no-flow conditions, amiloride increased internal and external diameters of carotid (13 ± 2%, P < 0.05) but not mesenteric (0.5 ± 0.9%, P > 0.05) arteries. In response to increased intraluminal pressure, amiloride had no effect on the internal diameter of either type of artery. However, amiloride affected the stress-strain curves of mesenteric arteries. With increased shear stress, ENaC-dependent effects were observed in both arteries. In carotid arteries, amiloride augmented flow-mediated dilation (9.2 ± 5.3%) compared with control (no amiloride, 6.2 ± 3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated constriction (−11.5 ± 6.6%) compared with control (−2.2 ± 4.5%, P < 0.05). l-NAME mimicked the effect of ENaC inhibition and prevented further amiloride effects in both types of arteries. These observations indicate that ENaC contributes to shear sensing in conduit and resistance arteries. ENaC-mediated effects were associated with NO production but may involve different (artery-dependent) downstream signaling pathways. NEW & NOTEWORTHY The epithelial Na+ channel (ENaC) contributes to shear sensing in conduit and resistance arteries. In conduit arteries ENaC has a role as a vasoconstrictor, whereas in resistance arteries ENaC contributes to vasodilation. Interaction of ENaC with endothelial nitric oxide synthase/nitric oxide signaling to mediate the effects is supported; however, cross talk with other shear stress-dependent signaling pathways cannot be excluded. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/different-roles-of-enac-in-carotid-and-mesenteric-arteries/ .

Myogenic regulation of arterial diameter: role of potassium channels with a focus on delayed rectifier potassium current

2005 ◽  
Vol 83 (8-9) ◽  
pp. 755-765 ◽  
Author(s):  
William C Cole ◽  
Tim T Chen ◽  
Odile Clément-Chomienne
Keyword(s):  
Potassium Channels ◽  
Molecular Mechanisms ◽  
Intraluminal Pressure ◽  
Delayed Rectifier ◽  
Resistance Arteries ◽  
Arterial Diameter ◽  
Resistance Vessels ◽  
Delayed Rectifier Potassium Current ◽  
Myogenic Regulation

The phenomenon of myogenic constriction of arterial resistance vessels in response to increased intraluminal pressure has been known for over 100 years, yet our understanding of the molecular mechanisms involved remains incomplete. The focus of this paper concerns the potassium (K+) channels that provide a negative feedback control of the myogenic depolarization of vascular smooth muscle cells that is provoked by elevations in intraluminal pressure, and specifically, the contribution of delayed rectifier (KDR) channels. Our knowledge of the important role played by KDR channels, as well as their molecular identity and acute modulation via changes in gating, has increased dramatically in recent years. Several lines of evidence point to a crucial contribution by heteromultimeric KV1 subunit-containing KDR channels in the control of arterial diameter and myogenic reactivity, but other members of the KV superfamily are also expressed by vascular myocytes, and less is known concerning their specific functions. The effect of pharmacological modulation of KDR channels is discussed, with particular reference to the actions of anorexinogens on KV1- and KV2-containing KDR channels. Finally, the need for a greater understanding of the mechanisms that control KDR channel gene expression is stressed in light of evidence indicating that there is a reduced expression of KDR channels in diseases associated with abnormal myogenic reactivity and vascular remodelling.Key words: resistance arteries, myogenic response, potassium channels, delayed rectifier K+ current, KV channels, KV1, KV2.

scholarly journals Structural remodeling of coronary resistance arteries: effects of age and exercise training

2014 ◽  
Vol 117 (6) ◽  
pp. 616-623 ◽  
Author(s):  
Mina A. Hanna ◽  
Curtis R. Taylor ◽  
Bei Chen ◽  
Hae-Sun La ◽  
Joshua J. Maraj ◽  
...  
Keyword(s):  
Exercise Training ◽  
Wall Thickness ◽  
Effective Elastic Modulus ◽  
Vascular Wall ◽  
Intraluminal Pressure ◽  
Coronary Resistance ◽  
Resistance Arteries ◽  
Fischer 344 ◽  
Wall Stiffness ◽  
Old Rats

Age is known to induce remodeling and stiffening of large-conduit arteries; however, little is known of the effects of age on remodeling and mechanical properties of coronary resistance arteries. We employed a rat model of aging to investigate whether 1) age increases wall thickness and stiffness of coronary resistance arteries, and 2) exercise training reverses putative age-induced increases in wall thickness and stiffness of coronary resistance arteries. Young (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of treadmill exercise training. Coronary resistance arteries were isolated for determination of wall-to-lumen ratio, effective elastic modulus, and active and passive responses to changes in intraluminal pressure. Elastin and collagen content of the vascular wall were assessed histologically. Wall-to-lumen ratio increased with age, but this increase was reversed by exercise training. In contrast, age reduced stiffness, and exercise training increased stiffness in coronary resistance arteries from old rats. Myogenic responsiveness was reduced with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of the wall did not change with age and was reduced with exercise training in arteries from old rats. Thus age induces hypertrophic remodeling of the vessel wall and reduces the stiffness and myogenic function of coronary resistance arteries. Exercise training reduces wall-to-lumen ratio, increases wall stiffness, and restores myogenic function in aged coronary resistance arteries. The restorative effect of exercise training on myogenic function of coronary resistance arteries may be due to both changes in vascular smooth muscle phenotype and expression of extracellular matrix proteins.

Spaceflight reduces vasoconstrictor responsiveness of skeletal muscle resistance arteries in mice

2012 ◽  
Vol 113 (9) ◽  
pp. 1439-1445 ◽  
Author(s):  
John N. Stabley ◽  
James M. Dominguez ◽  
Catherine E. Dominguez ◽  
Fredy R. Mora Solis ◽  
Joslyn Ahlgren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Contractile Activity ◽  
Intraluminal Pressure ◽  
Resistance Arteries ◽  
Vessel Wall Thickness ◽  
Physiological Capacity

Cardiovascular adaptations to microgravity undermine the physiological capacity to respond to orthostatic challenges upon return to terrestrial gravity. The purpose of the present study was to investigate the influence of spaceflight on vasoconstrictor and myogenic contractile properties of mouse gastrocnemius muscle resistance arteries. We hypothesized that vasoconstrictor responses acting through adrenergic receptors [norepinephrine (NE)], voltage-gated Ca2+ channels (KCl), and stretch-activated (myogenic) mechanisms would be diminished following spaceflight. Feed arteries were isolated from gastrocnemius muscles, cannulated on glass micropipettes, and physiologically pressurized for in vitro experimentation. Vasoconstrictor responses to intraluminal pressure changes (0–140 cmH2O), KCl (10–100 mM), and NE (10−9-10−4 M) were measured in spaceflown (SF; n = 11) and ground control (GC; n = 11) female C57BL/6 mice. Spaceflight reduced vasoconstrictor responses to KCl and NE; myogenic vasoconstriction was unaffected. The diminished vasoconstrictor responses were associated with lower ryanodine receptor-2 (RyR-2) and ryanodine receptor-3 (RyR-3) mRNA expression, with no difference in sarcoplasmic/endoplasmic Ca2+ ATPase 2 mRNA expression. Vessel wall thickness and maximal intraluminal diameter were unaffected by spaceflight. The data indicate a deficit in intracellular calcium release via RyR-2 and RyR-3 in smooth muscle cells as the mechanism of reduced contractile activity in skeletal muscle after spaceflight. Furthermore, the results suggest that impaired end-organ vasoconstrictor responsiveness of skeletal muscle resistance arteries contributes to lower peripheral vascular resistance and less tolerance of orthostatic stress in humans after spaceflight.

Exercise training alters myogenic responses in porcine coronary resistance arteries

1993 ◽  
Vol 75 (6) ◽  
pp. 2677-2682 ◽  
Author(s):  
J. M. Muller ◽  
P. R. Myers ◽  
M. H. Laughlin
Keyword(s):  
Exercise Training ◽  
Weight Ratio ◽  
Oxidative Capacity ◽  
Intraluminal Pressure ◽  
Heart Weight ◽  
Coronary Resistance ◽  
Resistance Arteries ◽  
Miniature Swine ◽  
Myogenic Responses

The purpose of this study was to test the hypothesis that myogenic responsiveness in porcine coronary resistance arteries is attenuated by exercise training. Twenty-four female Yucatan miniature swine were randomly separated into two groups of 12 pigs: exercise trained (ET) and sedentary control (SED). The ET pigs were trained on a motor-driven treadmill for 16–22 wk while the SED pigs remained confined to their pens. After training, heart weight-to-body weight ratio, skeletal muscle oxidative capacity, and exercise tolerance were significantly increased in ET pigs compared with SED pigs. Coronary resistance arteries 75–150 microns diam were isolated for in vitro evaluation of myogenic responses to changes in intraluminal pressure in the absence of intraluminal flow. Coronary resistance arteries from ET and SED pigs developed spontaneous tone at 40 mmHg intraluminal pressure. Active changes in diameter measured in response to intraluminal pressures < 40 mmHg were similar in coronary resistance arteries from ET and SED pigs. When pressure was raised above 40 mmHg, myogenic constriction was greater in coronary resistance arteries from ET pigs, as indicated by significantly greater reductions in diameter. At 60 and 70 mmHg intraluminal pressure, constriction was 8 and 16% greater, respectively, in resistance arteries from ET pigs. After maximal relaxation with sodium nitroprusside (100 microM), passive diameter changes measured in response to changes in intraluminal pressure from 10 to 80 mmHg were not significantly different in coronary resistance arteries from ET and SED pigs. We conclude that, contrary to our hypothesis, exercise training in pigs enhances myogenic constrictor responses in coronary resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Role of Actin Filament Dynamics in the Myogenic Response of Cerebral Resistance Arteries

2012 ◽  
Vol 33 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Michael P Walsh ◽  
William C Cole
Keyword(s):  
Light Chain ◽  
Actin Polymerization ◽  
Myosin Light Chain ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Intraluminal Pressure ◽  
Regulatory Subunit ◽  
Myogenic Response ◽  
Force Transmission ◽  
Resistance Arteries

The myogenic response has a critical role in regulation of blood flow to the brain. Increased intraluminal pressure elicits vasoconstriction, whereas decreased intraluminal pressure induces vasodilatation, thereby maintaining flow constant over the normal physiologic blood pressure range. Improved understanding of the molecular mechanisms underlying the myogenic response is crucial to identify deficiencies with pathologic consequences, such as cerebral vasospasm, hypertension, and stroke, and to identify potential therapeutic targets. Three mechanisms have been suggested to be involved in the myogenic response: (1) membrane depolarization, which induces Ca2+ entry, activation of myosin light chain kinase, phosphorylation of the myosin regulatory light chains (LC20), increased actomyosin MgATPase activity, cross-bridge cycling, and vasoconstriction; (2) activation of the RhoA/Rho-associated kinase (ROCK) pathway, leading to inhibition of myosin light chain phosphatase by phosphorylation of MYPT1, the myosin targeting regulatory subunit of the phosphatase, and increased LC20 phosphorylation; and (3) activation of the ROCK and protein kinase C pathways, leading to actin polymerization and the formation of enhanced connections between the actin cytoskeleton, plasma membrane, and extracellular matrix to augment force transmission. This review describes these three mechanisms, emphasizing recent developments regarding the importance of dynamic actin polymerization in the myogenic response of the cerebral vasculature.

scholarly journals Short-term regular aerobic exercise reduces oxidative stress produced by acute high intraluminal pressure in the adipose microvasculature

2017 ◽  
Vol 312 (5) ◽  
pp. H896-H906 ◽  
Author(s):  
Austin T. Robinson ◽  
Ibra S. Fancher ◽  
Varadarajan Sudhahar ◽  
Jing Tan Bian ◽  
Marc D. Cook ◽  
...  
Keyword(s):  
High Pressure ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Aerobic Exercise ◽  
Control Mouse ◽  
Vascular Dysfunction ◽  
Intraluminal Pressure ◽  
Ang Ii ◽  
Laminar Shear Stress ◽  
Resistance Arteries

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm2) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to H2O2. Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. NEW & NOTEWORTHY We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/exercise-averts-high-pressure-induced-vascular-dysfunction/ .

Sign in / Sign up

Export Citation Format

Share Document