scholarly journals TRPV1 in arteries enables a rapid myogenic tone

2022 ◽  
Author(s):  
Thieu X. Phan ◽  
Hoai T. Ton ◽  
Hajnalka Gulyás ◽  
Róbert Pórszász ◽  
Attila Tóth ◽  
...  
Keyword(s):  
Myogenic Tone

scholarly journals The control of Ca2+ influx and NFATc3 signaling in arterial smooth muscle during hypertension

2008 ◽  
Vol 105 (40) ◽  
pp. 15623-15628 ◽  
Author(s):  
Madeline Nieves-Cintrón ◽  
Gregory C. Amberg ◽  
Manuel F. Navedo ◽  
Jeffery D. Molkentin ◽  
Luis F. Santana
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Dysfunction ◽  
Signaling Cascade ◽  
Myogenic Tone ◽  
Excitable Cells ◽  
Open Probability ◽  
Induced Hypertension

Many excitable cells express L-type Ca2+ channels (LTCCs), which participate in physiological and pathophysiological processes ranging from memory, secretion, and contraction to epilepsy, heart failure, and hypertension. Clusters of LTCCs can operate in a PKCα-dependent, high open probability mode that generates sites of sustained Ca2+ influx called “persistent Ca2+ sparklets.” Although increased LTCC activity is necessary for the development of vascular dysfunction during hypertension, the mechanisms leading to increased LTCC function are unclear. Here, we tested the hypothesis that increased PKCα and persistent Ca2+ sparklet activity contributes to arterial dysfunction during hypertension. We found that PKCα and persistent Ca2+ sparklet activity is indeed increased in arterial myocytes during hypertension. Furthermore, in human arterial myocytes, PKCα-dependent persistent Ca2+ sparklets activated the prohypertensive calcineurin/NFATc3 signaling cascade. These events culminated in three hallmark signs of hypertension-associated vascular dysfunction: increased Ca2+ entry, elevated arterial [Ca2+]i, and enhanced myogenic tone. Consistent with these observations, we show that PKCα ablation is protective against the development of angiotensin II-induced hypertension. These data support a model in which persistent Ca2+ sparklets, PKCα, and calcineurin form a subcellular signaling triad controlling NFATc3-dependent gene expression, arterial function, and blood pressure. Because of the ubiquity of these proteins, this model may represent a general signaling pathway controlling gene expression and cellular function.

scholarly journals Pregnancy Causes Diminished Myogenic Tone and Outward Hypotrophic Remodeling of the Cerebral Vein of Galen

2013 ◽  
Vol 33 (4) ◽  
pp. 542-542 ◽  
Author(s):  
Anne-Eva van der Wijk ◽  
Malou PH Schreurs ◽  
Marilyn J Cipolla
Keyword(s):  
Cerebral Arteries ◽  
Venous Blood ◽  
Blood Stasis ◽  
Wall Stress ◽  
Myogenic Tone ◽  
Cerebral Vein ◽  
Cerebral Veins ◽  
Vein Of Galen ◽  
First Time ◽  
Serotonergic Innervation

Pregnancy increases the risk of several complications associated with the cerebral veins, including thrombosis and hemorrhage. In contrast to the cerebral arteries and arterioles, few studies have focused on the effect of pregnancy on the cerebral venous side. Here, we investigated for the first time the effect of pregnancy on the function and structure of the cerebral vein of Galen in rats. Our major finding was that cerebral veins from late-pregnant (LP, n = 11) rats had larger lumen diameters and thinner walls than veins from nonpregnant (NP, n = 13) rats, indicating that pregnancy caused outward hypotrophic remodeling of the vein of Galen. Moreover, veins from NP animals had a small amount of myogenic tone at 10 mm Hg (3.9 ± 1.0%) that was diminished in veins during pregnancy (0.8 ± 0.3%; P < 0.01). However, endothelium-dependent and -independent vasodilation of the veins was unchanged during pregnancy. Using immunohistochemistry, we show that the vein of Galen receives perivascular innervation, and that serotonergic innervation of cerebral veins is significantly higher in veins from LP animals. Outward hypotrophic remodeling and diminished tone of cerebral veins during pregnancy may contribute to the development of venous pathology through elevated wall tension and wall stress, and possibly by promoting venous blood stasis.

scholarly journals TRPM4 Channels Couple Purinergic Receptor Mechanoactivation and Myogenic Tone Development in Cerebral Parenchymal Arterioles

2014 ◽  
Vol 34 (10) ◽  
pp. 1706-1714 ◽  
Author(s):  
Yao Li ◽  
Rachael L Baylie ◽  
Matthew J Tavares ◽  
Joseph E Brayden
Keyword(s):  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Critical Role ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Receptor Activation ◽  
Myogenic Tone ◽  
Pial Arteries ◽  
Myogenic Regulation

Cerebral parenchymal arterioles (PAs) have a critical role in assuring appropriate blood flow and perfusion pressure within the brain. They are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to chemical stimulants, and enhanced myogenic tone development. The objective of the present study was to reveal some of the unique mechanisms of myogenic tone regulation in the cerebral microcirculation. Here, we report that in vivo suppression of TRPM4 (transient receptor potential) channel expression, or inhibition of TRPM4 channels with 9-phenanthrol substantially reduced myogenic tone of isolated PAs, supporting a key role of TRPM4 channels in PA myogenic tone development. Further, downregulation of TRPM4 channels inhibited vasoconstriction induced by the specific P2Y4 and P2Y6 receptor ligands (UTP γS and UDP) by 37% and 42%, respectively. In addition, 9-phenanthrol substantially attenuated purinergic ligand-induced membrane depolarization and constriction of PAs, and inhibited ligand-evoked TRPM4 channel activation in isolated PA myocytes. In concert with our previous work showing the essential contributions of P2Y4 and P2Y6 receptors to myogenic regulation of PAs, the current results point to TRPM4 channels as an important link between mechanosensitive P2Y receptor activation and myogenic constriction of cerebral PAs.

Enhanced resistance artery sensitivity to agonists under isobaric compared with isometric conditions

1994 ◽  
Vol 266 (1) ◽  
pp. H147-H155 ◽  
Author(s):  
W. R. Dunn ◽  
G. C. Wellman ◽  
J. A. Bevan
Keyword(s):  
Membrane Potential ◽  
Angiotensin Ii ◽  
Myogenic Tone ◽  
Isometric Contractions ◽  
Fundamental Interaction ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
Enhanced Resistance ◽  
Increased Sensitivity

We have compared the responsiveness of rabbit mesenteric resistance arteries with agonists under isometric and isobaric conditions. When pressurized (60 mmHg), arteries spontaneously reduced their diameter by 18.1%. An equivalent isometric stress did not generate force in a “wire” myograph. Subsequently, much higher concentrations of norepinephrine (NE) and histamine were required to cause isometric contractions than were needed to reduce vascular diameter of pressurized vessels, whereas angiotensin II produced a maintained response only in pressurized arteries. Reducing transmural pressure to 20 mmHg abolished pressure-induced myogenic tone and decreased arterial sensitivity to NE. Under isometric conditions, partial depolarization with KCl increased sensitivity to NE and histamine to within the concentration range effective in pressurized vessels and also "revealed" responses to angiotensin II. The membrane potential of the vascular smooth muscle cells under partially depolarized conditions was similar to that found in vivo and in vessels studied isobarically. These observations demonstrate a fundamental interaction between pressure-induced myogenic tone and the sensitivity of resistance arteries to vasoactive stimuli. This influence was mimicked in isometrically mounted vessels by partial depolarization, indicating a possible pivotal role for membrane potential in determining the reactivity of the resistance vasculature.

Vascular smooth muscle cell stress as a determinant of cerebral artery myogenic tone

2002 ◽  
Vol 283 (6) ◽  
pp. H2210-H2216 ◽  
Author(s):  
Johan Fredrik Brekke ◽  
Natalia I. Gokina ◽  
George Osol
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Wall Stress ◽  
Cytosolic Calcium ◽  
Cell Stress ◽  
Myogenic Tone ◽  
Vessel Size

Although the level of myogenic tone (MT) varies considerably from vessel to vessel, the regulatory mechanisms through which the actual diameter set point is determined are not known. We hypothesized that a unifying principle may be the equalization of active force at the contractile filament level, which would be reflected in a normalization of wall stress or, more specifically, media stress. Branched segments of rat cerebral arteries ranging from <50 μm to >200 μm in diameter were cannulated and held at 60 mmHg with the objectives of: 1) evaluating the relationship between arterial diameter and the extent of myogenic tone, 2) determining whether differences in MT correlate with changes in cytosolic calcium ([Ca2+]i), and 3) testing the hypothesis that a normalization of wall or media stress occurs during the process of tone development. The level of MT increased significantly as vessel size decreased. At 60 mmHg, vascular smooth muscle [Ca2+]i concentrations were similar in all vessels studied (averaging 230 ± 9.2 nM) and not correlated with vessel size or the extent of tone. Wall tension increased with increasing arterial size, but wall stress and media stress were similar in large versus small arteries. Media stress, in particular, was quite uniform in all vessels studied. Both morphological and calcium data support the concept of equalization of media stress (and, hence, vascular smooth muscle cell stress and force) as an underlying mechanism in determining the level of tone present in any particular vessel. The equalization of active (vascular smooth muscle cell) stress may thus explain differences in MT observed in the different-sized vessels constituting the arterial network and provide a link between arterial structure and function, in both short- and long-term (hypertension) pressure adaptation.

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

2005 ◽  
Vol 288 (4) ◽  
pp. H1756-H1762 ◽  
Author(s):  
Jacqueline Ohanian ◽  
Kelly M. Gatfield ◽  
Donald T. Ward ◽  
Vasken Ohanian
Keyword(s):  
Vascular Tissue ◽  
Immunoblot Analysis ◽  
Negative Regulator ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Calcium Sensing Receptor ◽  
Small Arteries ◽  
Calcium Sensing

Myogenic tone of small arteries is dependent on the presence of extracellular calcium ([Formula: see text]), and, recently, a receptor that senses changes in Ca2+, the calcium-sensing receptor (CaR), has been detected in vascular tissue. We investigated whether the CaR is involved in the regulation of myogenic tone in rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody against the CaR demonstrated its presence in rat subcutaneous arteries. To determine whether the CaR was functionally active, segments of artery (<250 μm internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing [Formula: see text] concentration ([Ca2+]o) cumulatively from 0.5 to 10 mM induced an initial constriction (0.5–2 mM) followed by dilation (42 ± 5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1–10 mM) and the aminoglycosides neomycin (0.003–10 mM) and kanamycin (0.003–3 mM). PKC activation with the phorbol ester phorbol-12,13-dibutyrate (20nM) inhibited the dilation induced by high [Ca2+]o or neomycin, whereas inhibition of PKC with GF109203X (10 μM) increased the responses to [Formula: see text] or neomycin, consistent with the role of PKC as a negative regulator of the CaR. We conclude that rat subcutaneous arteries express a functionally active CaR that may be involved in the modulation of myogenic tone and hence the regulation of peripheral vascular resistance.

Coronary artery myogenic response in a genetic model of hypertrophic cardiomyopathy

2002 ◽  
Vol 283 (6) ◽  
pp. H2244-H2249 ◽  
Author(s):  
Henrik H. Petersen ◽  
Jonathan Choy ◽  
Brian Stauffer ◽  
Farzad Moien-Afshari ◽  
Christian Aalkjaer ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Genetic Model ◽  
Morphological Characteristics ◽  
Myogenic Tone ◽  
Chain Gene ◽  
Myogenic Response ◽  
Cardiac Phenotype ◽  
First Time ◽  
Pressure Myograph ◽  
Intravascular Pressure

Hypertrophic cardiac myopathy (HCM) is the leading cause of mortality in young athletes. Abnormalities in small intramural coronary arteries have been observed at autopsy in such subjects. The walls of these intramural vessels, especially in the ventricular septum, are thickened, and the lumen frequently appears narrowed. Whether these morphological characteristics have functional correlates is unknown. We studied coronary myogenic tone in a transgenic mouse model of HCM that has mutations in the cardiac α-myosin heavy chain gene. This transgenic mouse has a cardiac phenotype that resembles that occurring in humans. We examined the possible vascular contributions to the pathology of HCM. Septal arteries from 3- and 11-mo-old wild-type (WT) and transgenic (TG) mice were studied on a pressure myograph. The myogenic response to increased intravascular pressure in older animals was significantly reduced [maximal constriction: 32 ± 4% (TG) and 46 ± 4% (WT), P < 0.05]. After inhibition of endothelin receptors with bosentan, both WT and TG mice had similar increases in myogenic constriction. The sensitivity to exogenous endothelin was significantly reduced in TG mice, suggesting that the reduced myogenic constriction in HCM was due to reduced receptor sensitivity. In conclusion, we show for the first time that 1) myogenic tone in the coronary septal artery of the mouse is regulated by a basal release of endothelin, and 2) pressure-induced myogenic activation is attenuated in HCM, possibly consequent to a reduction in endothelin responsiveness. The associated reduction in coronary vasodilatory reserve may increase susceptibility to ischemia and arrhythmias.

scholarly journals Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tumor Necrosis ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tnf Α ◽  
Necrosis Factor

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

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