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 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 SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch

2015 ◽  
Vol 37 (5) ◽  
pp. 1817-1829 ◽  
Author(s):  
Kai Huang ◽  
Zhi-Qiang Yan ◽  
Dan Zhao ◽  
Si-Guo Chen ◽  
Li-Zhi Gao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Underlying Mechanisms

Background/Aims: Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch. Methods and Results: Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect. Conclusion: Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.

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.

Abstract P183: Chemokine-like Receptor 1 Mediates the Vasoconstrictor Actions of Chemerin in vitro and in vivo

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Amanda Kennedy ◽  
Peiran Yang ◽  
Cai Read ◽  
Rhoda Kuc ◽  
Janet Maguire ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Therapeutic Potential ◽  
Plasma Concentrations ◽  
Resistance Arteries ◽  
Resistance Vessels ◽  
Increased Risk ◽  
First Time

Hypertensive patients have significantly higher plasma concentrations of the adipokine chemerin compared with healthy controls, and levels of chemerin positively correlate with systolic and diastolic blood pressure. Chemerin activates chemokine-like receptor 1 (CMKLR1 or ChemR23) but it also activates the ‘orphan’ G protein-coupled receptor 1 (GPR1) which has been linked with hypertension. It is therefore crucial to determine whether one or both of these receptors mediate the constrictor actions of chemerin in the vasculature in order to identify a potential new therapeutic target for the treatment of hypertension. Using immunohistochemistry and molecular biology, we localized chemerin to the endothelium, smooth muscle and adventitia, and CMKLR1 and GPR1 to the smooth muscle in human conduit and resistance vessels. Chemerin activated β-arrestin via heterologously expressed receptors GPR1 (pD 2 =9.30±0.05) and CMKLR1 (pD 2 =9.23±0.03) with comparable potency. CCX832, a small molecule antagonist, was fully characterized as highly selective for CMKLR1, with no effect on GPR1 in binding or cell-based functional assays. The C-terminal fragment of chemerin, C9 (chemerin149-157) contracted human saphenous vein (pD 2 =7.30±0.31) and resistance arteries (pD 2 =6.23±0.16), and caused a significant increase in blood pressure in rats in vivo (0.2 μmol, 9.1±1.0 mmHg). These actions were blocked by CCX832, confirming for the first time that a single chemerin receptor, CMKLR1, mediates the constrictor response in humans and in vivo. Our data suggest that chemerin activation of CMKLR1 may contribute to elevated blood pressure; this in combination with the known roles of chemerin in metabolic syndrome and diabetes, could lead to increased risk of cardiovascular disease. This study provides proof of principle that the therapeutic potential of selective CMKLR1 antagonists should be explored.

In vivo attenuation of endothelium-dependent pulmonary vasodilation by methylene blue

1991 ◽  
Vol 71 (2) ◽  
pp. 735-741 ◽  
Author(s):  
J. R. Fineman ◽  
M. R. Crowley ◽  
M. A. Heymann ◽  
S. J. Soifer
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Arterial Pressure ◽  
Guanylate Cyclase ◽  
Vascular Tone ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial

In vitro evidence suggests that resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in vascular smooth muscle concentrations of guanosine 3′,5′-cyclic monophosphate (cGMP). We investigated this hypothesis in vivo in 19 mechanically ventilated intact lambs by determining the hemodynamic effects of methylene blue (a guanylate cyclase inhibitor) and then by comparing the hemodynamic response to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimic) or methylene blue. Methylene blue caused a significant time-dependent increase in pulmonary arterial pressure. During U-46619 infusions, acetylcholine, ATP-MgCl2, sodium nitroprusside, isoproterenol, and 8-bromo-cGMP decreased pulmonary arterial pressure. During methylene blue infusions, the decreases in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) and sodium nitroprusside (an endothelium-independent guanylate cyclase-dependent vasodilator) were attenuated by greater than 50%. The decreases in pulmonary arterial pressure caused by isoproterenol and 8-bromo-cGMP (endothelium-independent vasodilators) were unchanged. This study in intact lambs supports the in vitro evidence that changes in vascular smooth muscle cell concentrations of cGMP in part mediate resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation.

scholarly journals Endothelium-Derived Hyperpolarizing Factor and Myoendothelial Coupling: The in vivo Perspective

2020 ◽  
Vol 11 ◽  
Author(s):  
Kjestine Schmidt ◽  
Cor de Wit
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Tone ◽  
Radial Spread ◽  
Distinct Features ◽  
Type Response ◽  
Chemical Mediators

The endothelium controls vascular tone adopting blood flow to tissue needs. It releases chemical mediators [e.g., nitric oxide (NO), prostaglandins (PG)] and exerts appreciable dilation through smooth muscle hyperpolarization, thus termed endothelium-dependent hyperpolarization (EDH). Initially, EDH was attributed to release of a factor, but later it was suggested that smooth muscle hyperpolarization might be derived from radial spread of an initial endothelial hyperpolarization through heterocellular channels coupling these vascular cells. The channels are indeed present and formed by connexins that enrich in gap junctions (GJ). In vitro data suggest that myoendothelial coupling underlies EDH-type dilations as evidenced by blocking experiments as well as simultaneous, merely identical membrane potential changes in endothelial and smooth muscle cells (SMCs), which is indicative of coupling through ohmic resistors. However, connexin-deficient animals do not display any attenuation of EDH-type dilations in vivo, and endothelial and SMCs exhibit distinct and barely superimposable membrane potential changes exerted by different means in vivo. Even if studied in the exact same artery EDH-type dilation exhibits distinct features in vitro and in vivo: in isometrically mounted vessels, it is rather weak and depends on myoendothelial coupling through connexin40 (Cx40), whereas in vivo as well as in vitro under isobaric conditions it is powerful and independent of myoendothelial coupling through Cx40. It is concluded that EDH-type dilations are distinct and a significant dependence on myoendothelial coupling in vitro does not reflect the situation under physiologic conditions in vivo. Myoendothelial coupling may act as a backup mechanism that is uncovered in the absence of the powerful EDH-type response and possibly reflects a situation in a pathophysiologic environment.

Smooth Muscle-Derived Nitric Oxide is Elevated in Isolated Forearm Veins in Human Alcoholic Cirrhosis

1996 ◽  
Vol 91 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Jeremy Ryan ◽  
Garry Jennings ◽  
Frank Dudley ◽  
Jaye Chin-Dusting
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Alcoholic Cirrhosis ◽  
Resistance Arteries ◽  
Nitric Oxide Synthase Inhibitor ◽  
Control Subjects ◽  
Synthase Inhibitor

1. Cirrhosis is often complicated by disturbances in the systemic circulation. We have previously demonstrated decreased vascular responses to vasoconstrictors in forearm resistance arteries in subjects with alcoholic cirrhosis. In the current study we investigate the role of the potent endogenous vasodilator nitric oxide in the peripheral circulation of these patients. 2. Ten patients with alcoholic cirrhosis (Pugh grade A) and 10 age-matched control subjects were studied. The effect of blockade of nitric oxide synthesis was studied both in vivo in forearm resistance arteries using forearm venous occlusion plethysmography and in vitro in veins isolated from the forearm. The role of endothelium-derived nitric oxide was studied in vivo using the endothelium-dependent vasodilator acetylcholine. 3. Mean arterial pressure and forearm basal flow in vivo were similar in the two groups. The constrictor response (percentage decrease in forearm blood flow) to noradrenaline (100 ng/min) was 26% smaller in patients with cirrhosis (31.65 ± 2.64%) than in control subjects (42.75 ± 3.87%, P = 0.037). Constrictor responses to the nitric oxide synthase inhibitor NG-monomethyl-l-arginine were not different in the two groups. Dilator responses to acetylcholine were significantly attenuated in cirrhotic patients compared with control subjects. 4. To investigate the role of smooth muscle-derived nitric oxide in vitro, all veins were stripped of their endothelium. Responses to noradrenaline were significantly diminished in veins isolated from patients with cirrhosis compared with control subjects. Incubation with the nitric oxide synthase inhibitor Nω-nitro-l-arginine had no effect on responses to noradrenaline in veins from control subjects but significantly enhanced the maximal response to noradrenaline by 23.95% (range 3.77–100%, P = 0.043) in veins from patients with cirrhosis. 5. Responses to noradrenaline were attenuated in vivo in forearm resistance arteries in patients with alcoholic cirrhosis. This impairment was also apparent in forearm isolated veins, stripped of the endothelium. Our data exclude a major role for endothelium-derived nitric oxide but highlight a possible role for smooth muscle-derived nitric oxide.

scholarly journals TRPV1 in arteries enables a rapid myogenic tone

2021 ◽  
Author(s):  
Thieu X Phan ◽  
Hoai T Ton ◽  
Hajnalka Gulyas ◽  
Robert Porszasz ◽  
Attila Toth ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Critical Role ◽  
Myogenic Tone ◽  
Dynamic Regulation ◽  
Membrane Stretch

Arterioles maintain blow flow by adjusting their diameter in response to changes in local blood pressure. In this process called the myogenic response, a vascular smooth muscle mechanosensor controls tone predominantly through altering the membrane potential. In general, myogenic responses occur slowly, reaching a plateau in minutes. In the heart and skeletal muscle, however, myogenic tone is rapid; activation occurs in tens of seconds and arterial constrictions or raised extravascular pressure as brief as 100 ms remove tone. Previously, we identified extensive expression of TRPV1 in the smooth muscle of arterioles supplying skeletal muscle, heart and the adipose. Here, we reveal a critical role for TRPV1 in the myogenic tone of these tissues. TRPV1 antagonists dilated skeletal muscle arterioles in vitro and in vivo , increased coronary flow in isolated hearts, and transiently decreased blood pressure. All of these effects of TRPV1 antagonists were abolished by genetic disruption of TRPV1. Stretch of isolated vascular smooth muscle cells, or raised intravascular pressure in arteries (with or without endothelium), triggered Ca2+ signaling and vasoconstriction. The majority of these stretch-responses were TRPV1-mediated, with the remaining tone being inhibited by the TRPM4 antagonist, 9-phenantrol. Notably, tone developed more quickly in arteries from wild-type compared with TRPV1-null mice. Furthermore, the rapid vasodilation following brief constriction of arterioles was also dependent on TRPV1, consistent with a rapid deactivation or inactivation of TRPV1. Pharmacologic experiments revealed that membrane stretch activates a phospholipase C/protein kinase C signaling pathway to activate TRPV1, and in turn, L-type Ca2+ channels. These results suggest a critical role, for TRPV1 in the dynamic regulation of myogenic tone and blood flow in the heart and skeletal muscle.

Regulation of fetal vascular tone in the human placenta

1991 ◽  
Vol 3 (4) ◽  
pp. 475 ◽  
Author(s):  
WA Walters ◽  
AL Boura
Keyword(s):  
Smooth Muscle ◽  
Prostaglandin E1 ◽  
Vascular Tone ◽  
Thromboxane A2 ◽  
High Sensitivity ◽  
Human Platelets ◽  
Perfusion Technique ◽  
A2 Receptors

Using an in vitro placental lobule perfusion technique, the human fetal placental vasculature has been found to respond vigorously with high sensitivity to various vasoconstrictor substances, including angiotensin II, endothelins 1 and 3, prostaglandins F2 alpha, E2 and D2 and the thromboxane A2 agonist U46619. Thromboxane A2 receptors mediating vasoconstriction have been characterized in fetal placental vessels and appear to be identical to those on human platelets and pulmonary blood vessels. Although the isolated fetal placental vessels are largely unresponsive to exogenous vasodilatory stimuli, when preconstricted they respond by vasodilatation to several vasodilator substances, including arachidonate, prostacyclin, prostaglandin E1, theophylline and nitroglycerine. The resistance offered to flow in vitro by the villous vasculature is therefore low, as it is in vivo. Both intrinsic and extrinsic mechanisms probably operate to cause relaxation of the vascular smooth muscle with the vasodilatory effects of locally released autacoids dominating the effects of those having vasoconstrictor actions.

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