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

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.

Download Full-text

Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.20 ◽

1991 ◽

Vol 11 (1) ◽

pp. 161-164 ◽

Cited By ~ 21

Author(s):

Mária Faragó ◽

Csaba Szabó ◽

Eörs Dóra ◽

Ildikó Horváth ◽

Arisztid G. B. Kovách

Keyword(s):

Smooth Muscle ◽

Vascular Reactivity ◽

Calcium Influx ◽

Cerebral Arteries ◽

Inhibitory Effect ◽

Contractile Responses ◽

Middle Cerebral Arteries ◽

The Right ◽

Endothelial Receptor

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

Download Full-text

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00542.2002 ◽

2002 ◽

Vol 283 (6) ◽

pp. H2268-H2275 ◽

Cited By ~ 27

Author(s):

Rebecca J. Coulson ◽

Naomi C. Chesler ◽

Lisa Vitullo ◽

Marilyn J. Cipolla

Keyword(s):

Contractile Activity ◽

Cerebral Arteries ◽

Biomechanical Properties ◽

Short Term ◽

Mechanical Stiffness ◽

Middle Cerebral Arteries ◽

Male Wistar Rats ◽

Myogenic Activity ◽

Activity Dependent

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

Download Full-text

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

The FASEB Journal ◽

10.1096/fasebj.20.5.a1113-b ◽

2006 ◽

Vol 20 (5) ◽

Author(s):

Alister James McNeish ◽

Kim Dora ◽

Chris Garland

Keyword(s):

Cerebral Arteries ◽

Myogenic Tone ◽

Middle Cerebral Arteries

Download Full-text

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00752.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1081-H1089 ◽

Cited By ~ 18

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.

Download Full-text

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.2.h610 ◽

2000 ◽

Vol 279 (2) ◽

pp. H610-H618 ◽

Cited By ~ 57

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.

Download Full-text

Impact of development and chronic hypoxia on NE release from adrenergic nerves in sheep arteries

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.3.r799 ◽

1999 ◽

Vol 276 (3) ◽

pp. R799-R808 ◽

Cited By ~ 7

Author(s):

John Buchholz ◽

Kim Edwards-Teunissen ◽

Sue P. Duckles

Keyword(s):

Chronic Hypoxia ◽

Cerebral Arteries ◽

Sensory Nerves ◽

Adrenergic Nerves ◽

Facial Artery ◽

Norepinephrine Release ◽

Differential Adaptation ◽

Middle Cerebral Arteries ◽

The Face

To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. N ω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity.

Download Full-text

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00253.2014 ◽

2014 ◽

Vol 117 (1) ◽

pp. 53-59 ◽

Cited By ~ 22

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.

Download Full-text

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00134.2011 ◽

2011 ◽

Vol 301 (1) ◽

pp. H29-H40 ◽

Cited By ~ 34

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.

Download Full-text

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00634.2002 ◽

2002 ◽

Vol 283 (6) ◽

pp. H2260-H2267 ◽

Cited By ~ 93

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.

Download Full-text