Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior

2002 ◽  
Vol 283 (6) ◽  
pp. H2260-H2267 ◽  
Author(s):  
George Osol ◽  
Johan Fredrik Brekke ◽  
Keara McElroy-Yaggy ◽  
Natalia I. Gokina
Keyword(s):  
Cerebral Arteries ◽  
Peripheral Resistance ◽  
Force Production ◽  
Cytosolic Calcium ◽  
Myogenic Tone ◽  
Wall Tension ◽  
Resistance Arteries ◽  
Cellular Mechanisms ◽  
Initial Development

Myogenic behavior, prevalent in resistance arteries and arterioles, involves arterial constriction in response to intravascular pressure. This process is often studied in vitro by using cannulated, pressurized arterial segments from different regional circulations. We propose a comprehensive model for myogenicity that consists of three interrelated but dissociable phases: 1) the initial development of myogenic tone (MT), 2) myogenic reactivity to subsequent changes in pressure (MR), and 3) forced dilatation at high transmural pressures (FD). The three phases span the physiological range of transmural pressures (e.g., MT, 40–60 mmHg; MR, 60–140 mmHg; FD, >140 mmHg in cerebral arteries) and are characterized by distinct changes in cytosolic calcium ([Ca2+]i), which do not parallel arterial diameter or wall tension, and therefore suggest the existence of additional regulatory mechanisms. Specifically, the development of MT is accompanied by a substantial (200%) elevation in [Ca2+]i and a reduction in lumen diameter and wall tension, whereas MR is associated with relatively small [Ca2+]i increments (<20% over the entire pressure range) despite considerable increases in wall tension and force production but little or no change in diameter. FD is characterized by a significant additional elevation in [Ca2+]i (>50%), complete loss of force production, and a rapid increase in wall tension. The utility of this model is that it provides a framework for comparing myogenic behavior of vessels of different size and anatomic origin and for investigating the underlying cellular mechanisms that govern vascular smooth muscle mechanotransduction and contribute to the regulation of peripheral resistance.

scholarly journals Circadian Rhythmicity in Cerebral Microvascular Tone Influences Subarachnoid Hemorrhage–Induced Injury

Stroke ◽  
2021 ◽  
Author(s):  
Darcy Lidington ◽  
Hoyee Wan ◽  
Danny D. Dinh ◽  
Chloe Ng ◽  
Steffen-Sebastian Bolz
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Circadian Rhythms ◽  
Cerebral Arteries ◽  
Circadian Variation ◽  
Neurological Injury ◽  
Myogenic Tone ◽  
Resistance Arteries

Background and Purpose: Circadian rhythms influence the extent of brain injury following subarachnoid hemorrhage (SAH), but the mechanism is unknown. We hypothesized that cerebrovascular myogenic reactivity is rhythmic and explains the circadian variation in SAH-induced injury. Methods: SAH was modeled in mice with prechiasmatic blood injection. Inducible, smooth muscle cell–specific Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1) gene deletion (smooth muscle–specific Bmal1 1 knockout [sm-Bmal1 KO]) disrupted circadian rhythms within the cerebral microcirculation. Olfactory cerebral resistance arteries were functionally assessed by pressure myography in vitro; these functional assessments were related to polymerase chain reaction/Western blot data, brain histology (Fluoro-Jade/activated caspase-3), and neurobehavioral assessments (modified Garcia scores). Results: Cerebrovascular myogenic vasoconstriction is rhythmic, with a peak and trough at Zeitgeber times 23 and 11 (ZT23 and ZT11), respectively. Histological and neurobehavioral assessments demonstrate that higher injury levels occur when SAH is induced at ZT23, compared with ZT11. In sm-Bmal1 KO mice, myogenic reactivity is not rhythmic. Interestingly, myogenic tone is higher at ZT11 versus ZT23 in sm-Bmal1 KO mice; accordingly, SAH-induced injury in sm-Bmal1 KO mice is more severe when SAH is induced at ZT11 compared to ZT23. We examined several myogenic signaling components and found that CFTR (cystic fibrosis transmembrane conductance regulator) expression is rhythmic in cerebral arteries. Pharmacologically stabilizing CFTR expression in vivo (3 mg/kg lumacaftor for 2 days) eliminates the rhythmicity in myogenic reactivity and abolishes the circadian variation in SAH-induced neurological injury. Conclusions: Cerebrovascular myogenic reactivity is rhythmic. The level of myogenic tone at the time of SAH ictus is a key factor influencing the extent of injury. Circadian oscillations in cerebrovascular CFTR expression appear to underlie the cerebrovascular myogenic reactivity rhythm.

scholarly journals Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms

2000 ◽  
Vol 279 (2) ◽  
pp. H610-H618 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Cerebral Arteries ◽  
Gonadal Hormones ◽  
No Synthase ◽  
Male Rats ◽  
Male Rat ◽  
Myogenic Tone ◽  
Channel Blockers ◽  
Luminal Diameter ◽  
Nos Inhibitor

Gender is known to influence the incidence and severity of cerebrovascular disease. In the present study, luminal diameter was measured in vitro in pressurized middle cerebral artery segments from male rats that were either untreated, orchiectomized (ORX), ORX with testosterone treatment (ORX+TEST), or ORX with estrogen treatment (ORX+EST). The maximal passive diameters (0 Ca2+ + 3 mM EDTA) of arteries from all four groups were similar. In endothelium-intact arteries, myogenic tone was significantly greater in arteries from untreated and ORX+TEST compared with arteries from either ORX or ORX+EST. During exposure to N G-nitro-l-arginine-methyl ester (l-NAME), an NO synthase (NOS) inhibitor, myogenic tone significantly increased in all groups. The effect of l-NAME was significantly greater in arteries from untreated and ORX+EST compared with arteries from ORX and ORX+TEST rats. Differences in myogenic tone between ORX and ORX+TEST persisted after inhibition of NOS. After endothelium removal or inhibition of the cyclooxygenase pathway combined with K+ channel blockers, myogenic tone differences between ORX and ORX+TEST were abolished. Wall thickness and forced dilation were not significantly different between arteries from ORX and ORX+TEST. Our data show that gonadal hormones affect myogenic tone in male rat cerebral arteries through NOS- and/or endothelium-dependent mechanisms.

scholarly journals Myogenic contractility is more dependent on myofilament calcium sensitization in term fetal than adult ovine cerebral arteries

2007 ◽  
Vol 293 (1) ◽  
pp. H548-H556 ◽  
Author(s):  
Renan J. Sandoval ◽  
Elisha R. Injeti ◽  
James M. Williams ◽  
William T. Georthoffer ◽  
William J. Pearce
Keyword(s):  
Calcium Influx ◽  
Cerebral Arteries ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Stretch Ratio ◽  
Myogenic Tone ◽  
Postnatal Maturation ◽  
Calcium Sensitization ◽  
Myofilament Calcium Sensitivity ◽  
Krebs Buffer

Regulation of cytosolic calcium and myofilament calcium sensitivity varies considerably with postnatal age in cerebral arteries. Because these mechanisms also govern myogenic tone, the present study used graded stretch to examine the hypothesis that myogenic tone is less dependent on calcium influx and more dependent on myofilament calcium sensitization in term fetal compared with adult cerebral arteries. Term fetal and adult posterior communicating cerebral arteries exhibited similar myogenic responses, with peak tensions averaging 24 and 26% of maximum contractile force produced in any given tissue in response to an isotonic Krebs buffer containing 122 mM K+ (Kmax) at optimum stretch ratios (working diameter/unstressed diameter) of 2.19 and 2.23, respectively. Graded stretch increased cytosolic Ca2+ concentration at stretch ratios >2.0 in adult arteries, but increased Ca2+ concentration only at stretch ratios >2.3 in fetal arteries. In permeabilized arteries, myogenic tone peaked at a stretch ratio of 2.1 in both fetal and adult arteries. The fetal %Kmax values at peak myogenic tone were not significantly different at either pCa 7.0 (23%) or pCa 5.5 (25%) but were significantly less at pCa 8.0 (8.4 ± 2.3%). Conversely, adult %Kmax values at peak myogenic tone were significantly less at both pCa 8.0 (10.4 ± 1.8%) and pCa 7.0 (16%) than at pCa 5.5 (27%). The maximal extents of stretch-induced increases in myosin light chain phosphorylation in intact fetal (20%) and adult (17%) arteries were similar. The data demonstrate that the cerebrovascular myogenic response is highly conserved during postnatal maturation but is mediated differently in fetal and adult cerebral arteries.

scholarly journals Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity

2014 ◽  
Vol 117 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Marilyn J. Cipolla ◽  
Julie Sweet ◽  
Siu-Lung Chan ◽  
Matthew J. Tavares ◽  
Natalia Gokina ◽  
...  
Keyword(s):  
Ion Channel ◽  
Small Vessel Disease ◽  
Cerebral Arteries ◽  
Calcium Sensitivity ◽  
Cytosolic Calcium ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Contractile Apparatus ◽  
Pial Arteries ◽  
Middle Cerebral Arteries

Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs ( P < 0.01), and VSM calcium was 200 ± 20 nmol/l in PAs vs. 104 ± 15 nmol/l in MCAs ( P < 0.01). In vessels permeabilized with Staphylococcus aureus α-toxin, PAs were not more sensitive to calcium, suggesting calcium sensitization was not at the level of the contractile apparatus. PAs were 30-fold more sensitive to the voltage-dependent calcium channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs; P < 0.01); however, electrophysiological properties of the VDCC were not different in VSM. PAs had little to no response to the calcium-activated potassium channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

scholarly journals Myogenic Vasoconstriction Requires Canonical Gq/11 Signaling of the Angiotensin II Type 1a Receptor in the Murine Vasculature

2020 ◽  
Author(s):  
Yingqiu Cui ◽  
Mario Kassmann ◽  
Sophie Nickel ◽  
Chenglin Zhang ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Signaling Pathways ◽  
G Protein ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Myogenic Response ◽  
Ang Ii ◽  
Resistance Arteries ◽  
Renal Vasculature ◽  
Downstream Signaling

AbstractBackgroundThe myogenic response is an inherent vasoconstrictive property of resistance arteries to keep blood flow constant in response to increases in intravascular pressure. Angiotensin II (Ang II) type 1 receptors (AT1R) are broadly distributed, mechanoactivated receptors, which have been proposed to transduce myogenic vasoconstriction. However, the AT1R subtype(s) involved and their downstream G protein- and β-arrestin-mediated signaling pathways are still elusive.ObjectiveTo characterize the function of AT1aR and AT1bR in the regulation of the myogenic response of resistance size arteries and possible downstream signaling cascades mediated by Gq/11 and/or β-arrestins.MethodsWe used Agtr1a-/-, Agtr1b-/- and tamoxifen-inducible smooth muscle-specific AT1aR knockout mice (SM-Agtr1a mice). FR900359, [Sar1, Ile4, Ile8] Ang II (SII) and TRV120055 were used as selective Gq/11 protein inhibitor and biased agonists to activate non-canonical β-arrestin and canonical Gq/11 signaling of the AT1R, respectively.ResultsMyogenic and Ang II-induced vasoconstrictions were diminished in the perfused renal vasculature of Agtr1a-/- and SM-Agtr1a mice. Similar results were observed in isolated pressurized mesenteric and cerebral arteries. Myogenic tone and Ang II-induced vasoconstrictions were normal in arteries from Agtr1b-/- mice. The Gq/11 blocker FR900359 decreased myogenic tone and Ang II vasoconstrictions while selective biased targeting of AT1R β-arrestin signaling pathways had no effects.ConclusionThe present study demonstrates that myogenic arterial constriction requires Gq/11-dependent signaling pathways of mechanoactivated AT1aR but not G protein-independent, noncanonical alternative signaling pathways in the murine mesenteric, cerebral and renal circulation.

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage

2002 ◽  
Vol 283 (6) ◽  
pp. H2217-H2225 ◽  
Author(s):  
Masanori Ishiguro ◽  
Corey B. Puryear ◽  
Erica Bisson ◽  
Christine M. Saundry ◽  
David J. Nathan ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Rabbit Model ◽  
Small Diameter ◽  
Myogenic Tone ◽  
The Impact ◽  
Intravascular Pressure

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100–200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (∼twofold) to pressure within the physiological range of 60–100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.

Contrasting effects of simulated microgravity with and without daily −Gx gravitation on structure and function of cerebral and mesenteric small arteries in rats

2009 ◽  
Vol 107 (6) ◽  
pp. 1710-1721 ◽  
Author(s):  
Le-Jian Lin ◽  
Fang Gao ◽  
Yun-Gang Bai ◽  
Jun-Xiang Bao ◽  
Xiao-Feng Huang ◽  
...  
Keyword(s):  
Structural Changes ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Small Arteries ◽  
Functional Studies ◽  
Cell Layers ◽  
And Function

This study was designed to test the hypothesis that a 28-day tail suspension (SUS) could induce hypertrophy and enhanced myogenic and vasoconstrictor reactivity in middle cerebral arteries (MCAs), whereas atrophy and decreased myogenic and vasoconstrictor responses in mesenteric third-order arterioles (MSAs). Also, in addition to the functional enhancement in MCAs, structural changes in both kinds of arteries and functional decrement in MSAs could all be prevented by the intervention of daily 1-h dorsoventral (−Gx) gravitation by restoring to standing posture. To test this hypothesis, vessel diameters to pressure alterations and nonreceptor- and receptor-mediated agonists were determined using a pressure arteriograph with a procedure to measure in vivo length and decrease hysteresis of vessel segments and longitudinal middlemost sections of vessels fixed at maximally dilated state were examined using electron microscopy and histomorphometry. Functional studies showed that 28-day tail-suspended, head-down tilt (SUS) resulted in enhanced and decreased myogenic tone and vasoconstrictor responses, respectively, in MCAs and MSAs. Histomorphometric data revealed that SUS-induced hypertrophic changes in MCAs characterized by increases in thickness (T) and cross-sectional area (CSA) of the media and the number of vascular smooth-muscle-cell layers (NCL), whereas in MSAs, it induced decreases in medial CSA and T and NCL. Daily 1-h −Gx over 28 days can fully prevent these differential structural changes in both kinds of small arteries and the functional decrement in MSAs, but not the augmented myogenic tone and increased vasoreactivity in the MCAs. These findings have revealed special features of small resistance arteries during adaptation to microgravity with and without gravity-based countermeasure.

Force-velocity relationship of myogenically active arterioles

2002 ◽  
Vol 282 (1) ◽  
pp. H165-H174 ◽  
Author(s):  
Michael J. Davis ◽  
Judy Davidson
Keyword(s):  
Smooth Muscle ◽  
Maximum Velocity ◽  
Cheek Pouch ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Wall Tension ◽  
Shortening Velocity ◽  
Hamster Cheek Pouch ◽  
Velocity Of Shortening

We compared the shortening velocity of smooth muscle in arterioles that had low or high levels of myogenic tone or norepinephrine (NE)-induced tone. We hypothesized that enhanced myogenic tone of arterioles reflects an enhanced maximum velocity of shortening of arteriolar smooth muscle in a way that is different from that produced by NE. These concepts are untested assumptions of arteriolar mechanics. Second-order arterioles from hamster cheek pouch (passive diameter at 40 mmHg = 42 μm) were isolated and cannulated for in vitro study. In the absence of flow, pressure was controlled by hydraulic pumps so that servo control of wall tension could be achieved from measurement of internal diameter and pressure. Isotonic quick-release protocols were used to measure the initial velocity of shortening following release from control wall tension (afterload) to a series of fractional afterloads. After release, the initial rates of shortening were fit to the Hill equation to obtain coefficients for a hyperbolic fit of the velocity-afterload relationship. The maximal unloaded shortening velocity for partially activated arterioles ( V′max) was determined from the y-intercept of each plot. Using this procedure, we compared V′max from two groups of arterioles equilibrated at low or high pressure, i.e., with low or high myogenic tone. Arterioles with higher myogenic tone had higher values of V′max than arterioles with lower myogenic tone. V′max for arterioles partially activated with NE at low pressure was comparable to V′max for arterioles with high myogenic tone, but NE produced high velocities at low force, whereas enhanced myogenic tone produced roughly parallel shifts in velocity and force. The results suggest that increased myogenic tone does indeed reflect enhanced activation of arteriolar smooth muscle, and this effect is mechanically different from that produced by NE.

Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries

1998 ◽  
Vol 275 (1) ◽  
pp. H292-H300 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
Myogenic Tone ◽  
No Production ◽  
Luminal Diameter ◽  
Underlying Mechanisms ◽  
Synthase Inhibitor ◽  
Endothelial Nitric Oxide ◽  
Dependent Mechanism

Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production. Luminal diameter was measured in middle cerebral artery segments from males and from females that were either untreated, ovariectomized (Ovx), or ovariectomized with estrogen replacement (Ovx + Est). The maximal passive diameters (0 Ca2++ 1 mM EDTA) of arteries from all four groups were identical. In response to a series of 10-mmHg step increases in transmural pressure (20–80 mmHg), myogenic tone was greater and vascular distensibility less in arteries from males and Ovx females compared with arteries from either untreated or Ovx + Est females. In the presence of N G-nitro-l-arginine methyl ester (l-NAME; 1 μM), an NO synthase inhibitor, myogenic tone was increased in all arteries, but the differences among arteries from the various groups were abolished. Addition ofl-arginine (1 mM) in the presence of l-NAME restored the differences in myogenic tone, suggesting that estrogen works through an NO-dependent mechanism in cerebral arteries. To determine the target of NO-dependent modulation of myogenic tone, we used tetraethylammonium (TEA; 1 mM) to inhibit large-conductance, calcium-activated K+(BKCa) channels. In the presence of TEA, the myogenic tone of arteries from all groups increased significantly; however, myogenic tone in arteries from males and Ovx females remained significantly greater than in arteries from either untreated or Ovx + Est females. This suggests that activity of BKCa channels influences myogenic tone but does not directly mediate the effects of estrogen. Estrogen appears to alter myogenic tone by increasing cerebrovascular NO production and/or action.

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