Modulation of myogenic responsiveness by CO2 in rat diaphragmatic arterioles: role of the endothelium

1997 ◽  
Vol 272 (3) ◽  
pp. H1419-H1425 ◽  
Author(s):  
M. M. Nagi ◽  
M. E. Ward
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Intraluminal Pressure ◽  
Negative Slope ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Myogenic Response ◽  
Inhibitory Mechanisms ◽  
Flow Through

The effect of hypercapnia on the myogenic response was determined in arterioles (80- to 100-microm internal diameter) isolated from the diaphragms of rats killed by decapitation. All arterioles were exposed to step changes in intraluminal pressure over a range of 10-200 mmHg and had no flow through their lumen. In five separate groups of vessels (n = 7 per group), PCO2 of the superfusing buffer was adjusted to 40, 60, 80, 90, or 100 mmHg. In three further groups of vessels (n = 7 per group), the endothelium was removed by low-pressure air perfusion (2 ml at 20 mmHg) and PCO2 of the superfusing buffer was adjusted to 40, 80, or 100 mmHg. In endothelium-intact vessels, increasing PCO2 to 80 mmHg enhanced the myogenic response, as reflected by a negative slope of the pressure-diameter relationship (slope = -0.164 +/- 0.03 vs. 0.004 +/- 0.02 for vessels at PCO2 = 40 mmHg, P < 0.05). With a PCO2 of 100 mmHg, dilation accompanied increasing intraluminal pressure and the slope of the pressure-diameter curve was positive (0.154 +/- 0.03, P < 0.05 for difference from vessels at PCO2 = 40 mmHg). In deendothelialized vessels, the curve was shifted upward in a parallel manner during exposure to increased PCO2 levels. Moderate hypercapnia (PCO2 < 80 mmHg) elicits endothelium-dependent enhancement of myogenic tone. Severe hypercapnia (PCO2 > 80 mmHg) inhibits myogenic tone through a direct effect on vascular smooth muscle and through endothelium-dependent inhibitory mechanisms.

Evidence for a functional calcium-sensing receptor that modulates myogenic tone in rat subcutaneous small arteries

2005 ◽  
Vol 288 (4) ◽  
pp. H1756-H1762 ◽  
Author(s):  
Jacqueline Ohanian ◽  
Kelly M. Gatfield ◽  
Donald T. Ward ◽  
Vasken Ohanian
Keyword(s):  
Vascular Tissue ◽  
Immunoblot Analysis ◽  
Negative Regulator ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Calcium Sensing Receptor ◽  
Small Arteries ◽  
Calcium Sensing

Myogenic tone of small arteries is dependent on the presence of extracellular calcium ([Formula: see text]), and, recently, a receptor that senses changes in Ca2+, the calcium-sensing receptor (CaR), has been detected in vascular tissue. We investigated whether the CaR is involved in the regulation of myogenic tone in rat subcutaneous small arteries. Immunoblot analysis using a monoclonal antibody against the CaR demonstrated its presence in rat subcutaneous arteries. To determine whether the CaR was functionally active, segments of artery (<250 μm internal diameter) mounted in a pressure myograph with an intraluminal pressure of 70 mmHg were studied after the development of myogenic tone. Increasing [Formula: see text] concentration ([Ca2+]o) cumulatively from 0.5 to 10 mM induced an initial constriction (0.5–2 mM) followed by dilation (42 ± 5% loss of tone). The dose-dependent dilation was mimicked by other known CaR agonists including magnesium (1–10 mM) and the aminoglycosides neomycin (0.003–10 mM) and kanamycin (0.003–3 mM). PKC activation with the phorbol ester phorbol-12,13-dibutyrate (20nM) inhibited the dilation induced by high [Ca2+]o or neomycin, whereas inhibition of PKC with GF109203X (10 μM) increased the responses to [Formula: see text] or neomycin, consistent with the role of PKC as a negative regulator of the CaR. We conclude that rat subcutaneous arteries express a functionally active CaR that may be involved in the modulation of myogenic tone and hence the regulation of peripheral vascular resistance.

Myogenic responses of isolated rat skeletal muscle venules: modulation by norepinephrine and endothelium

1996 ◽  
Vol 271 (1) ◽  
pp. H267-H272 ◽  
Author(s):  
G. Dornyei ◽  
E. Monos ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptor ◽  
Perfusion Pressure ◽  
Receptor Activation ◽  
Intraluminal Pressure ◽  
Negative Slope ◽  
Internal Diameter ◽  
Myogenic Response ◽  
First Order ◽  
Diameter Curve

The pressure-induced myogenic response of large venules of skeletal muscle and its possible interactions with adrenergic receptor activation and endothelial factors have not yet been elucidated. Therefore, first-order venules of rat gracilis muscle were isolated, cannulated, and placed in an organ chamber. Changes in internal diameter of the vessels as a function of perfusion pressure (PP) were obtained. In response to increases in PP (0.5-17.5 mmHg), the diameter of venules increased from 197.1 +/- 23.96 to 369 +/- 14.1 microns. In passive conditions (in Ca(2+)-free solution), the pressure-diameter curve of venules shifted significantly upward. In the presence of norepinephrine (NE; 10(-6) M) in the bath solution, the pressure-diameter curve of active venules shifted significantly downward, and in the pressure-normalized diameter curve, a negative slope developed (-6.1 +/- 4.6). In both the absence and presence of NE, removal of endothelium significantly reduced venular diameters in the pressure ranges of 3-5 and 2-5 mmHg, respectively, but did not change significantly the characteristics of the pressure-diameter curves. These findings indicate that the smooth muscle of venules actively responds to changes in intraluminal pressure. This response is greatly facilitated by NE and modulated by the endothelium. The myogenic response of skeletal muscle venules, especially in the presence of NE, could have a role in the regulation of the resistance and capacitance of venules and, consequently, blood flow and tissue exchange in skeletal muscle.

scholarly journals Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature

2020 ◽  
Vol 318 (2) ◽  
pp. H461-H469 ◽  
Author(s):  
Evan Yamasaki ◽  
Pratish Thakore ◽  
Vivek Krishnan ◽  
Scott Earley
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Ang Ii ◽  
Pial Arteries

Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments. NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.

scholarly journals Peroxynitrite diminishes myogenic tone in cerebral arteries: role of nitrotyrosine and F-actin

2007 ◽  
Vol 292 (2) ◽  
pp. H1042-H1050 ◽  
Author(s):  
Matthew J. Maneen ◽  
Marilyn J. Cipolla
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cerebral Arteries ◽  
Fold Increase ◽  
Myogenic Tone ◽  
Ischemia And Reperfusion Injury ◽  
Tetraethylammonium Chloride ◽  
Male Wistar Rats ◽  
Subsequent Loss

This study investigated the effect of peroxynitrite (OONO−)-induced nitrosylation of filamentous (F)-actin on myogenic tone in isolated and pressurized posterior cerebral arteries (PCAs). Immunohistochemical staining was used to determine 3-nitrotyrosine (NT) and F-actin content in vascular smooth muscle after exposure to 10−7 M or 10−4 M OONO− for 5 or 60 min in isolated third-order PCAs ( n = 37) from male Wistar rats pressurized to 75 mmHg in an arteriograph chamber, quantified with confocal microscopy. Additionally, the role of K+ channels in OONO−-induced dilation was investigated with 3 μM glibenclamide or 10 mM tetraethylammonium chloride before OONO− exposure. OONO− (10−4 M) induced a 40% dilation of tone ( P < 0.05) while diminishing F-actin content by half ( P < 0.05) and causing a 60-fold increase in NT ( P < 0.05) in the vascular smooth muscle of PCAs. Additionally, F-actin was inversely correlated with both diameter and NT content ( P < 0.05) and was significantly colocalized in the vascular smooth muscle with NT (overlap coefficient = 0.8). The dilation to ONOO− was independent of K+ channel activity and thiol oxidation as glibenclamide, tetraethylammonium chloride, and dithiothreitol had no effect on OONO−-induced dilation or F-actin or NT content in PCAs. Because NT was colocalized with F-actin, we hypothesize that OONO− induces nitrosylation of F-actin in vascular smooth muscle leading to depolymerization and the subsequent loss of myogenic tone, which may promote vascular damage during oxidative stress such as in ischemia and reperfusion injury.

Vascular smooth muscle calcium waves in isolated arterioles : interactions between intraluminal pressure and intracellular calcium handling

2010 ◽  
Author(s):  
◽  
Srikanth Reddy Ella
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Physiological Role ◽  
Wave Activity ◽  
Calcium Handling ◽  
Intraluminal Pressure ◽  
General Level ◽  
Control Element ◽  
Myogenic Response ◽  
Ip3 Receptors

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Arterioles, an important control element in the circulatory system regulate blood flow in part though a phenomenon known as the 'Myogenic Response'. Myogenic response of small vessels is their ability to constrict in response to increase in intraluminal pressure or conversely dilate in response to a reduction in pressure. Calcium (Ca[superscript 2+]) is an important and essential signaling element for myogenic constriction. Apart from steady elevations in smooth muscle intracellular Ca[superscript 2+] in response to agonists or intraluminal pressure, several local and temporal Ca[superscript 2+] events such as sparks, waves, flashes also exist. These temporal Ca[superscript 2+] events are differentially regulated in several vascular beds and are poorly understood. Therefore, the current project aimed to understand the effects of intraluminal pressure on arteriolar vascular smooth muscle Ca+ waves in rat cremaster muscle arterioles. The project aimed to investigate the mechanisms underlying the generation of Ca[superscript 2+] waves and postulate a possible physiological role for the Ca[superscript 2+] waves. Increases in intraluminal pressure increased the Ca[superscript 2+] wave activity, described by the number of cells exhibiting Ca[superscript 2+] waves and their frequency. Ca[superscript 2+] waves occurred due to the activation of the IP3 receptors present on the sarcoplasmic reticulum in the cells. The presence of Ca[superscript 2+] waves in the smooth muscle cells provided a general level of vascular activation, wherein the wave activity is modulated to change the temporal responses of the myogenic behaviour. Elimination of Ca[superscript 2+] waves delayed the myogenic constriction, while increased Ca[superscript 2+] wave activity fastened the myogenic constriction.--From public.pdf

Vascular ENaC proteins are required for renal myogenic constriction

2005 ◽  
Vol 289 (4) ◽  
pp. F891-F901 ◽  
Author(s):  
Nikki L. Jernigan ◽  
Heather A. Drummond
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Sensory Neurons ◽  
Intraluminal Pressure ◽  
Induced Responses ◽  
Molecular Identity ◽  
Renal Vessels ◽  
Mechanosensitive Ion Channel ◽  
Renal Blood Flow Autoregulation

The myogenic response is an essential component of renal blood flow autoregulation and is the inherent ability of vascular smooth muscle cells (VSMCs) to contract in response to increases in intraluminal pressure. Although mechanosensitive ion channels are thought to initiate VSMC stretch-induced contraction, their molecular identity is unknown. Recent reports suggest degenerin/epithelial Na+ channels (DEG/ENaC) may form mechanotransducers in sensory neurons and VSMCs; however, the role of DEG/ENaC proteins in myogenic constriction of mouse renal arteries has not been established. To test the hypothesis that DEG/ENaC proteins are required for myogenic constriction in renal vessels, we first determined expression of ENaC transcripts and proteins in mouse renal VSMCs. Then, we determined pressure- and agonist-induced constriction and changes in vascular smooth muscle cytosolic Ca2+ and Na+ in isolated mouse renal interlobar arteries following DEG/ENaC inhibition with amiloride and benzamil. We detect α-, β-, and γENaC transcript and protein expression in cultured mouse renal VSMC. In contrast, we detect only β- and γ- but not αENaC protein in freshly dispersed mrVMSC. Selective DEG/ENaC inhibition, with low doses of amiloride and benzamil, abolishes pressure-induced constriction and increases in cytosolic Ca2+ and Na+ without diminishing agonist-induced responses in isolated mouse interlobar arteries. Our findings indicate that DEG/ENaC proteins are required for myogenic constriction in mouse interlobar arteries and are consistent with our hypothesis that DEG/ENaC proteins may be components of mechanosensitive ion channel complexes required for myogenic vasoconstriction.

Integrins and mechanotransduction of the vascular myogenic response

2001 ◽  
Vol 280 (4) ◽  
pp. H1427-H1433 ◽  
Author(s):  
Michael J. Davis ◽  
Xin Wu ◽  
Timothy R. Nurkiewicz ◽  
Junya Kawasaki ◽  
George E. Davis ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Tone ◽  
Vascular Wall ◽  
Matrix Proteins ◽  
Myogenic Response ◽  
Integrin Subunit ◽  
General Role ◽  
Mitogen Activated Protein

This review summarizes what is currently known about the role of integrins in the vascular myogenic response. The myogenic response is the rapid and maintained constriction of a blood vessel in response to pressure elevation. A role for integrins in this process has been suggested because these molecules form an important mechanical link between the extracellular matrix and the vascular smooth muscle cytoskeleton. We briefly summarize evidence for a general role of integrins in mechanotransduction. We then describe the integrin subunit combinations known to exist in smooth muscle and the vascular wall matrix proteins that may interact with these integrins. We then discuss the effects of integrin-specific peptides and antibodies on vascular tone and on calcium entry mechanisms in vascular smooth muscle. Because integrin function is linked to the cytoskeleton, we discuss evidence for the role of the cytoskeleton in determining myogenic responsiveness. Finally, we analyze evidence that integrin-linked signaling pathways, such as those involving protein tyrosine phosphorylation cascades and mitogen-activated protein kinases, are required for myogenic tone.

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