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.

Effect of Propofol on Norepinephrine-induced Increases in [Ca2+](i) and Force in Smooth Muscle of the Rabbit Mesenteric Resistance Artery 

1998 ◽  
Vol 88 (6) ◽  
pp. 1566-1578 ◽  
Author(s):  
Nami Imura ◽  
Yoshihisa Shiraishi ◽  
Hirotada Katsuya ◽  
Takeo Itoh
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
High K ◽  
Small Resistance ◽  
Vasodilating Activity ◽  
Mesenteric Resistance Artery

Background Propofol (2,6-diisopropylphenol) possesses vasodilating activity in vivo and in vitro. The propofol-induced relaxation of agonist-induced contractions in small resistance arteries has not been clarified. Methods The effect of propofol was examined on the contractions induced by norepinephrine and high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and isometric force in ryanodine-treated strips. Results Propofol attenuated the contractions induced by high K+ and norepinephrine, the effect being greater on the high K+-induced contraction than on the norepinephrine-induced contraction. In Ca2+-free solution, norepinephrine produced a transient contraction resulting from the release of Ca2+ from storage sites that propofol attenuated. In ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In the presence of nicardipine, propofol had no inhibitory action on the residual norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased resting [Ca2+]i, as in the absence of nicardipine. Conclusions In smooth muscle of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine-induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly as a result of an inhibition of [Ca2+]i removal mechanisms. These results may explain in part the variety of actions seen with propofol in various types of vascular smooth muscle.

scholarly journals Myogenic Tone in Peripheral Resistance Arteries and Arterioles: The Pressure Is On!

2021 ◽  
Vol 12 ◽  
Author(s):  
William F. Jackson
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Steady State ◽  
Vascular Smooth Muscle ◽  
Signaling Pathways ◽  
Vascular Resistance ◽  
Myogenic Tone ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
Fluid Exchange

Resistance arteries and downstream arterioles in the peripheral microcirculation contribute substantially to peripheral vascular resistance, control of blood pressure, the distribution of blood flow to and within tissues, capillary pressure, and microvascular fluid exchange. A hall-mark feature of these vessels is myogenic tone. This pressure-induced, steady-state level of vascular smooth muscle activity maintains arteriolar and resistance artery internal diameter at 50–80% of their maximum passive diameter providing these vessels with the ability to dilate, reducing vascular resistance, and increasing blood flow, or constrict to produce the opposite effect. Despite the central importance of resistance artery and arteriolar myogenic tone in cardiovascular physiology and pathophysiology, our understanding of signaling pathways underlying this key microvascular property remains incomplete. This brief review will present our current understanding of the multiple mechanisms that appear to underlie myogenic tone, including the roles played by G-protein-coupled receptors, a variety of ion channels, and several kinases that have been linked to pressure-induced, steady-state activity of vascular smooth muscle cells (VSMCs) in the wall of resistance arteries and arterioles. Emphasis will be placed on the portions of the signaling pathways underlying myogenic tone for which there is lack of consensus in the literature and areas where our understanding is clearly incomplete.

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.

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.

Intravascular pressure and diameter profile of the utero-ovarian resistance artery network: estrous cycle-dependent modulation of resistance artery tone

2007 ◽  
Vol 293 (5) ◽  
pp. H2937-H2944 ◽  
Author(s):  
Terrence E. Sweeney ◽  
Pooneh Bagher ◽  
Jocelyn Bailey ◽  
Salvatore J. Cherra ◽  
Frank N. Grisafi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Estrous Cycle ◽  
Cycle Phase ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
Vascular Regulation ◽  
Cycle Dependent ◽  
Intravascular Pressure

Blood flow to the ovary varies dramatically in both magnitude and distribution throughout the estrous cycle to meet the hormonal and metabolic demands of the ovarian parenchyma as it cyclically develops and regresses. Several vascular components appear to be critical to vascular regulation of the ovary. As a first step in resolving the role of the resistance arteries and their paired veins in regulating ovarian blood flow and transvascular exchange, we characterized the architecture and intravascular pressure profile of the utero-ovarian resistance artery network in an in vivo preparation of the ovary of the anesthetized Golden hamster. We also investigated estrous cycle-dependent changes in resistance artery tone. The right ovary and the cranial aspect of the uterus in 26 female hamsters were exposed for microcirculatory observations. Estrous-cycle phase was determined in each animal before experimentation. The utero-ovarian vascular architecture was determined and resistance artery diameters were measured in each animal by video microscopy. Servo-null intravascular pressure measurements were made throughout the uteroovarian arterial network in 11 of the animals. Architectural data showed a complex anastomotic network jointly supplying the uterus and ovary. Resistance arteries showed a high degree of coiling and close apposition to veins, maximizing countercurrent-exchange capabilities. Arterial pressure dropped below 60% of systemic arterial pressure before the arteries entered the ovary. Both the ovarian artery and the uterine artery, which jointly feed the ovary, showed cycle day-dependent changes in diameter. Arterial diameters were smallest on the day following ovulation, during the brief luteal phase of the hamster. The data show that resistance arteries comprise a critical part of a complex network designed for intimate local communication and control and suggest that these arteries may play an important role in regulating ovarian blood flow in an estrous cycle-specific manner.

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 Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction

2018 ◽  
Vol 314 (5) ◽  
pp. H1053-H1060 ◽  
Author(s):  
Karima Ait-Aissa ◽  
Andrew O. Kadlec ◽  
Joseph Hockenberry ◽  
David D. Gutterman ◽  
Andreas M. Beyer
Keyword(s):  
Cardiovascular Disease ◽  
Angiotensin Ii ◽  
Reverse Transcriptase ◽  
Microvascular Dysfunction ◽  
Telomerase Reverse Transcriptase ◽  
Telomerase Rna ◽  
Ang Ii ◽  
Resistance Arteries ◽  
Novel Target

A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO’s vasodilator and anti-inflammatory effects. Although primarily studied in larger conduit arteries, excess ROS release and a corresponding loss of NO also occur in smaller resistance arteries of the microcirculation, but the underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II). We report that genetic loss of TERT [maximal dilation: 52.0 ± 6.1% with vehicle, 60.4 ± 12.9% with Nω-nitro-l-arginine methyl ester (l-NAME), and 32.2 ± 12.2% with polyethylene glycol-catalase (PEG-Cat) ( P < 0.05), means ± SD, n = 9–19] but not TERC [maximal dilation: 79 ± 5% with vehicle, 10.7 ± 9.8% with l-NAME ( P < 0.05), and 86.4 ± 8.4% with PEG-Cat, n = 4–7] promotes flow-induced ROS formation. Moreover, TERT knockout exacerbates the microvascular dysfunction resulting from in vivo ANG II treatment, whereas TERT overexpression is protective [maximal dilation: 88.22 ± 4.6% with vehicle vs. 74.0 ± 7.3% with ANG II (1,000 ng·kg−1·min−1) ( P = not significant), n = 4]. Therefore, loss of TERT but not TERC may be a key contributor to the elevated microvascular ROS levels and reduced peak dilation observed in several cardiovascular disease pathologies. NEW & NOTEWORTHY This study identifies telomerase reverse transcriptase (TERT) but not telomerase RNA component as a key factor regulating endothelium-dependent dilation in the microcirculation. Loss of TERT activity leads to microvascular dysfunction but not conduit vessel dysfunction in first-generation mice. In contrast, TERT is protective in the microcirculation in the presence of prolonged vascular stress. Understanding the mechanism of how TERT protects against vascular stress represents a novel target for the treatment of vascular disorders.

Stretch-dependent (myogenic) tone in rabbit ear resistance arteries

1986 ◽  
Vol 250 (1) ◽  
pp. H87-H95 ◽  
Author(s):  
J. J. Hwa ◽  
J. A. Bevan
Keyword(s):  
Smooth Muscle ◽  
Vascular Tone ◽  
Mechanical Stretch ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Physiological Regulation ◽  
Rabbit Ear ◽  
Arterial Tone

Rabbit ear resistance arteries are vessels with three to six layers of smooth muscle cells and an unstretched lumen diameter of 75-150 micron. Ring segments of these arteries, in response to mechanical stretch in vitro, developed a maintained tonic contraction. The stretch-dependent contraction achieved a plateau within 10-30 min. Smooth muscle relaxants, such as NaNO2 and papaverine, substitution of extracellular Ca2+ by subthreshold Ca2+ (25 microM), or exposure to the Ca2+ influx antagonist Mn2+ abolished the stretch-dependent tone. The extent of the tone was dependent on the level of the applied stretch and the extracellular Ca2+ concentration ( [Ca2+]o). The maximal tone developed at optimal stretch, and [Ca2+]o in the bath solution was 18.1 +/- 4.6% of the maximal contraction of the vessel to histamine. This level of tone is comparable to neurogenic tone developed in response to nerve stimulation within the physiological frequency range. The stretch-dependent tone is considered probably myogenic in origin, since it was present in arterial segments that had been chronically denervated by surgical sympathectomy, mechanically deprived of the endothelium, and multireceptor blocked (phenoxybenzamine, 10(-6) M). Our findings suggest first that the stretch-dependent tone is myogenic and may be similar to basal vascular tone arising from the stretch of arterial pressure and its changes in vivo. Second, the magnitude of myogenic tone is a function of the applied stretch and the [Ca2+]o. Finally, myogenic tone is important in the physiological regulation of arterial tone in the rabbit ear resistance arteries.

scholarly journals Signaling of angiotensin II-induced vascular protein synthesis in conduit and resistance arteries in vivo

2004 ◽  
Vol 4 (1) ◽  
Author(s):  
Christine Daigle ◽  
Fabrice MAC Martens ◽  
Daphné Girardot ◽  
Huy Hao Dao ◽  
Rhian M Touyz ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Angiotensin Ii ◽  
Resistance Arteries

A nimodipine-resistant Ca2+ pathway is involved in myogenic tone in a resistance artery

1986 ◽  
Vol 251 (1) ◽  
pp. H182-H189 ◽  
Author(s):  
J. J. Hwa ◽  
J. A. Bevan
Keyword(s):  
Endothelial Cells ◽  
Sympathetic Nerves ◽  
Inhibitory Effect ◽  
Myogenic Tone ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
High K ◽  
Rabbit Ear ◽  
Local Release

After stretch, tone develops in ring segments of rabbit ear resistance arteries (75-150 micron unstretched lumen diam). This is myogenic tone, since it is not dependent on the presence of sympathetic nerves, endothelial cells, or the local release of any known vasoactive autacoids. It is sensitive to the extracellular Ca2+ concentration, and disappears in a low Ca2+ (25 microM) environment. Tone is restored immediately on the reintroduction of Ca2+ (0.1-1.6 mM). High K+-induced tone in these resistance arteries is also extracellular Ca2+-dependent. The Ca2+ ED50 of this tone is 2.45 X 10(-4) M, which is significantly lower than that for myogenic tone (Ca2+ ED50; 8.31 X 10(-4) M). Both tone moieties are influenced by inorganic Ca2+ antagonists (Mn2+ and Mg2+) and some organic Ca2+ antagonists (verapamil and diltiazem). Among all the Ca2+ antagonists studied, only Mn2+ completely inhibits myogenic tone. In contrast, myogenic tone is resistant to nimodipine (up to 10(-6) M), the most potent Ca2+ antagonist of K+-induced contraction (ID50; 1.0 X 10(-9) M). Other 1,4-dihydropyridine Ca2+ antagonists such as nifedipine and (-)-PN 200-110 selectively antagonize K+-induced contractions, whereas they do not affect the development and the maintenance of myogenic tone. The fact that the (+)-enantiomer of PN 200-110 does not have an inhibitory effect proves that the 1,4-DHP site is stereospecific. These results indicate that extracellular Ca2+ is essential for both stretch-dependent (myogenic) and K+-induced tone, and the Ca2+ entry pathways for the two tone moieties are differently influenced by dihydropyridines.

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