scholarly journals NO can suppress myogenic tone in rat middle cerebral arteries by activating BK Ca

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Alister James McNeish ◽  
Kim Dora ◽  
Chris Garland
Keyword(s):  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Middle Cerebral Arteries

Sex-specific differences in cerebral arterial myogenic tone in hypertensive and normotensive rats

2006 ◽  
Vol 290 (3) ◽  
pp. H1081-H1089 ◽  
Author(s):  
Jamila Ibrahim ◽  
Ann McGee ◽  
Delyth Graham ◽  
John C. McGrath ◽  
Anna F. Dominiczak
Keyword(s):  
Blood Flow ◽  
Cerebral Arteries ◽  
Systemic Blood Pressure ◽  
Limiting Factors ◽  
Myogenic Tone ◽  
Spontaneously Hypertensive ◽  
Cerebrovascular Events ◽  
Middle Cerebral Arteries ◽  
Wistar Kyoto ◽  
Strain Dependent

Cerebral blood flow (CBF) is maintained constant despite changes in systemic blood pressure (BP) through multiple mechanisms of autoregulation such as vascular myogenic reactivity. Our aim was to determine myogenic characteristics of cannulated middle cerebral arteries (MCA) in male and female stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) at 12 wk of age under pressurised no-flow conditions. MCA pressure-diameter relationships (20–200 mmHg) were constructed in active (with calcium) and passive (without calcium) conditions, and myogenic and mechanical properties were determined. Myogenic reactivity in WKY ( P < 0.05) and SHRSP ( P < 0.05) males was impaired compared with their female counterparts. Comparison of SHRSP with WKY in males revealed similar myogenic reactivity, but in females SHRSP exhibited augmented myogenic reactivity ( P < 0.05). In both sexes, myogenic tone yielded at lower pressure in SHRSP compared with WKY vessels (120–140 vs. 140–180 mmHg). Stress-strain relationships and elastic moduli in WKY rats showed that vessels were stiffer in females than in males. Conversely, in SHRSP, male vessels were stiffer than female vessels. Comparison of strains in males indicated that stiffness was increased in SHRSP compared with WKY vessels, whereas the converse was observed in females. These findings demonstrate that MCA myogenic and distensibility characteristics exhibit significant sex- and strain-dependent differences. Inappropriate myogenic adaptation and augmented vascular stiffness, particularly in male SHRSP, are potential limiting factors in blood flow autoregulation and may increase the predisposition for stroke-related cerebrovascular events.

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 Differential effects of diet-induced obesity on BKCa β1-subunit expression and function in rat skeletal muscle arterioles and small cerebral arteries

2011 ◽  
Vol 301 (1) ◽  
pp. H29-H40 ◽  
Author(s):  
Lauren Howitt ◽  
Shaun L. Sandow ◽  
T. Hilton Grayson ◽  
Zoe E. Ellis ◽  
Margaret J. Morris ◽  
...  
Keyword(s):  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Cremaster Muscle ◽  
Α Subunit ◽  
Differential Effects ◽  
Subunit Protein ◽  
Diet Induced Obesity ◽  
Middle Cerebral Arteries ◽  
Subunit Expression ◽  
And Function

Mechanisms underlying obesity-related vascular dysfunction are unclear. This study examined the effect of diet-induced obesity on expression and function of large conductance Ca2+-activated potassium channel (BKCa) in rat pressurized small resistance vessels with myogenic tone. Male Sprague-Dawley rats fed a cafeteria-style high fat diet (HFD; ∼30% energy from fat) for 16–20 wk were ∼30% heavier than controls fed standard chow (∼13% fat). Obesity did not alter BKCa α-subunit function or α-subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BKCa β1-subunit protein expression and function were significantly reduced in cremaster muscle arterioles but increased in middle-cerebral arteries from obese animals. Immunohistochemistry showed α- and β1-subunits were present exclusively in the smooth muscle of both vessels. Cremaster muscle arterioles from obese animals showed significantly increased medial thickness, and media-to-lumen ratio and pressurized arterioles showed increased myogenic tone at 30 mmHg, but not at 50–120 mmHg. Myogenic tone was not affected by obesity in middle-cerebral arteries. The BKCa antagonist iberiotoxin constricted both cremaster muscle and middle-cerebral arterioles from control rats; this effect of iberiotoxin was abolished in cremaster muscle arteries only from obese rats. Diet-induced obesity has contrasting effects on BKCa function in different vascular beds, through differential effects on β1-subunit expression. However, these alterations in BKCa function had little effect on overall myogenic tone, suggesting that the mechanisms controlling myogenic tone can be altered and compensate for altered BKCa expression and function.

Nonspecific Inhibition of Myogenic Tone by PD98059, a MEK1 Inhibitor, in Rat Middle Cerebral Arteries

1999 ◽  
Vol 257 (2) ◽  
pp. 523-527 ◽  
Author(s):  
Guy.J.L. Lagaud ◽  
Eugene Lam ◽  
Amy Lui ◽  
Cornelis van Breemen ◽  
Ismail Laher
Keyword(s):  
Cerebral Arteries ◽  
Myogenic Tone ◽  
Middle Cerebral Arteries

scholarly journals Redox Signaling via Oxidative Inactivation of PTEN Modulates Pressure-Dependent Myogenic Tone in Rat Middle Cerebral Arteries

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68498 ◽  
Author(s):  
Debebe Gebremedhin ◽  
Maia Terashvili ◽  
Nadi Wickramasekera ◽  
David X. Zhang ◽  
Nicole Rau ◽  
...  
Keyword(s):  
Cerebral Arteries ◽  
Redox Signaling ◽  
Myogenic Tone ◽  
Oxidative Inactivation ◽  
Middle Cerebral Arteries

Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice

2008 ◽  
Vol 294 (4) ◽  
pp. H1793-H1803 ◽  
Author(s):  
Kimberly P. Gannon ◽  
Lauren G. VanLandingham ◽  
Nikki L. Jernigan ◽  
Samira C. Grifoni ◽  
Gina Hamilton ◽  
...  
Keyword(s):  
Ion Channel ◽  
Sensory Neurons ◽  
Knockout Mice ◽  
Cerebral Arteries ◽  
Normal Pressure ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Wild Type ◽  
Middle Cerebral Arteries

Recent studies from our laboratory demonstrated the importance of mechanosensitive epithelial Na+ channel (ENaC) proteins in pressure-induced constriction in renal and cerebral arteries. ENaC proteins are closely related to acid-sensing ion channel 2 (ASIC2), a protein known to be required for normal mechanotransduction in certain sensory neurons. However, the role of the ASIC2 protein in pressure-induced constriction has never been addressed. The goal of the current study was to investigate the role of ASIC2 proteins in pressure-induced, or myogenic, constriction in the mouse middle cerebral arteries (MCAs) from ASIC2 wild-type (+/+), heterozygous (+/−), and null (−/−) mice. Constrictor responses to KCl (20–80 mM) and phenylephrine (10−7–10−4 M) were not different among groups. However, vasoconstrictor responses to increases in intraluminal pressure (15–90 mmHg) were impaired in MCAs from ASIC2−/− and +/− mice. At 60 and 90 mmHg, MCAs from ASIC2+/+ mice generated 13.7 ± 2.1% and 15.8 ± 2.0% tone and ASIC2−/− mice generated 7.4 ± 2.8% and 12.5 ± 2.4% tone, respectively. Surprisingly, MCAs from ASIC2+/− mice generated 1.2 ± 2.2% and 3.9 ± 1.8% tone at 60 and 90 mmHg. The reason underlying the total loss of myogenic tone in the ASIC2+/− is not clear, although the loss of mechanosensitive β- and γ-ENaC proteins may be a contributing factor. These results demonstrate that normal ASIC2 expression is required for normal pressure-induced constriction in the MCA. Furthermore, ASIC2 may be involved in establishing the basal level of myogenic tone.

scholarly journals Intracellular Acidification Alters Myogenic Responsiveness and Vasomotion of Mouse Middle Cerebral Arteries

2013 ◽  
Vol 34 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Axel BK Thomsen ◽  
Sukhan Kim ◽  
Filip Aalbaek ◽  
Christian Aalkjaer ◽  
Ebbe Boedtkjer
Keyword(s):  
Knockout Mice ◽  
Kinase Inhibitor ◽  
Cerebral Arteries ◽  
Rho Kinase ◽  
Vascular Wall ◽  
Mesenteric Arteries ◽  
Myogenic Tone ◽  
No Production ◽  
Wild Type ◽  
Middle Cerebral Arteries

Intracellular pH (pHi) in the vascular wall modulates agonist-induced vasocontractile and vasorelaxant responses in mesenteric arteries, whereas effects on myogenic tone have been unsettled. We studied the role of Na+,HCO3− cotransporter NBCn1 in mouse isolated middle cerebral arteries and the influence of pHi disturbances on myogenic tone. Na+,HCO3− cotransport was abolished in arteries from NBCn1 knockout mice and steady-state pHi ∼0.3 units reduced compared with wild-type mice. Myogenic tone development was low under control conditions but increased on treatment with the NO-synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME). This effect of L-NAME was smaller in arteries from NBCn1 knockout than wild-type mice. Myogenic tone with L-NAME present was significantly lower in arteries from NBCn1 knockout than wild-type mice and was abolished by rho-kinase inhibitor Y-27632. The arteries displayed vasomotion, and this rhythmic contractile pattern was also attenuated in arteries from NBCn1 knockout mice. No differences in membrane potential or intracellular [Ca2+] were seen between arteries from NBCn1 knockout and wild-type mice. We propose that NO production and rho-kinase-dependent Ca2+ sensitivity are reduced at low pHi in pressurized mouse middle cerebral arteries. This likely impedes the ability to adjust to changes in perfusion pressure and regulate cerebral blood flow.

scholarly journals Aging Impairs Myogenic Adaptation to Pulsatile Pressure in Mouse Cerebral Arteries

2015 ◽  
Vol 35 (4) ◽  
pp. 527-530 ◽  
Author(s):  
Zsolt Springo ◽  
Peter Toth ◽  
Stefano Tarantini ◽  
Nicole M Ashpole ◽  
Zsuzsanna Tucsek ◽  
...  
Keyword(s):  
High Pressure ◽  
Cerebral Arteries ◽  
Distal Portion ◽  
Myogenic Tone ◽  
Myogenic Response ◽  
Pressure Waves ◽  
Cerebral Microcirculation ◽  
Microvascular Damage ◽  
Pulsatile Pressure ◽  
Middle Cerebral Arteries

Stability of myogenic tone in middle cerebral arteries (MCA) is essential for adequate control over penetration of pressure waves into the distal portion of the cerebral microcirculation. Because the increased pulse pressure observed in advanced aging is associated with cerebromicrovascular injury, the effect of aging on myogenic response of mouse MCAs was determined. Aging did not affect the myogenic constriction in response to static increases in pressure, whereas it significantly impaired pulsatile pressure-induced myogenic tone. Impaired myogenic adaptation of MCAs to pulsatile pressure may allow high pressure to penetrate the distal portion of the cerebral microcirculation, contributing to microvascular damage.

Mechanical Properties of Rat Middle Cerebral Arteries With and Without Myogenic Tone

2004 ◽  
Vol 126 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Marilyn J. Cipolla ◽  
Lisa Vitullo ◽  
Naomi C. Chesler
Keyword(s):  
Vessel Wall ◽  
Cerebral Arteries ◽  
Passive State ◽  
Myogenic Tone ◽  
Drug Induced ◽  
Elasticity Parameter ◽  
Wall Stiffness ◽  
Middle Cerebral Arteries ◽  
Inner Diameter

The inner diameter and wall thickness of rat middle cerebral arteries (MCAs) were measured in vitro in both a pressure-induced, myogenically-active state and a drug-induced, passive state to quantify active and passive mechanical behavior. Elasticity parameters from the literature (stiffness derived from an exponential pressure-diameter relationship, β, and elasticity in response to an increment in pressure, Einc-p) and a novel elasticity parameter in response to smooth muscle cell (SMC) activation, Einc-a, were calculated. β for all passive MCAs was 9.11±1.07 but could not be calculated for active vessels. The incremental stiffness increased significantly with pressure in passive vessels; Einc-p 106 dynes/cm2 increased from 5.6±0.5 at 75 mmHg to 14.7±2.4 at 125 mmHg, (p<0.05). In active vessels, Einc-p 106 dynes/cm2 remained relatively constant (5.5±2.4 at 75 mmHg and 6.2±1.0 at 125 mmHg). Einc-a 106 dynes/cm2 increased significantly with pressure (from 15.1±2.3 at 75 mmHg to 49.4±12.6 at 125 mmHg, p<0.001), indicating a greater contribution of SMC activity to vessel wall stiffness at higher pressures.

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