Role of T-type calcium channels in myogenic tone of skeletal muscle resistance arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2239-H2243 ◽  
Author(s):  
Ed VanBavel ◽  
Oana Sorop ◽  
Ditte Andreasen ◽  
Martin Pfaffendorf ◽  
Boye L. Jensen
Keyword(s):  
Calcium Channels ◽  
Southern Blotting ◽  
Myogenic Tone ◽  
Cremaster Muscle ◽  
Resistance Arteries ◽  
Rt Pcr ◽  
Response Curves ◽  
Potent Effect ◽  
Channel Expression

T-type calcium channels may be involved in the maintenance of myogenic tone. We tested their role in isolated rat cremaster arterioles obtained after CO2anesthesia and decapitation. Total RNA was analyzed by RT-PCR and Southern blotting for calcium channel expression. We observed expression of voltage-operated calcium (CaV) channels CaV3.1 (T-type), CaV3.2 (T-type), and CaV1.2 (L-type) in cremaster arterioles ( n= 3 rats). Amplification products were observed only in the presence of reverse transcriptase and cDNA. Concentration-response curves of the relatively specific L-type blocker verapamil and the relatively specific T-type blockers mibefradil and nickel were made on cannulated vessels with either myogenic tone (75 mmHg) or a similar level of constriction induced by 30 mM K+ at 35 mmHg. Mibefradil and nickel were, respectively, 162-fold and 300-fold more potent in inhibiting myogenic tone compared with K+-induced constriction [log(IC50, M): mibefradil, basal −7.3 ± 0.2 ( n = 9) and K+ −5.1 ± 0.1 ( n = 5); nickel, basal −4.1 ± 0.2 ( n = 5) and K+ −1.6 ± 0.5 ( n = 5); means ± SE]. Verapamil had a 17-fold more potent effect [log(IC50, M): basal −6.6 ± 0.1 ( n = 5); K+ −5.4 ± 0.3 ( n = 4); all log(IC50) P < 0.05, basal vs. K+]. These data suggest that T-type calcium channels are expressed and involved in maintenance of myogenic tone in rat cremaster muscle arterioles.

Correlation between mRNA levels and functional role of α1-adrenoceptor subtypes in arteries: evidence of α1L as a functional isoform of the α1A-adrenoceptor

2005 ◽  
Vol 289 (5) ◽  
pp. H1923-H1932 ◽  
Author(s):  
Daniel Martí ◽  
Raquel Miquel ◽  
Khalid Ziani ◽  
Regina Gisbert ◽  
M. Dolores Ivorra ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Mesenteric Arteries ◽  
Main Role ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Response Curves ◽  
Inhibitory Potency ◽  
Adrenoceptor Antagonist ◽  
Relevant Role

The mRNA levels for the three α1-adrenoceptor subtypes, α1A, α1B, and α1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The α1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), α1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both α1A- and α1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the α1B-subtype were a minority in all vessels (1.7–11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to α1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 μmol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspiro ( 4 , 5 ) decane-7-dionedihydrochloride} (BMY-7378, an α1D-adrenoceptor antagonist) confirm the relevant role of α1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an α1A-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of α1A- and α1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of α1A/α1L-adrenoceptors with minor participation of the α1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the α1L-adrenoceptor could be a functional isoform of the α1A-subtype.

scholarly journals PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries

2015 ◽  
Vol 308 (12) ◽  
pp. H1517-H1524 ◽  
Author(s):  
Joseph R. H. Mauban ◽  
Joseph Zacharia ◽  
Seth Fairfax ◽  
Withrow Gil Wier
Keyword(s):  
Specific Inhibitor ◽  
Intrinsic Property ◽  
Tissue Perfusion ◽  
Pressure Control ◽  
Mesenteric Arteries ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Virtual Absence ◽  
Sphingomyelin Synthase

Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K+ concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP3, we investigated the effect of blocking IP3 receptor-mediated Ca2+ release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca2+ waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca2+ concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP3 are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and/or SM synthase, is likely through multiple mechanisms to increase Ca2+ entry and promote vasoconstriction.

Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries

1999 ◽  
Vol 277 (4) ◽  
pp. H1546-H1552 ◽  
Author(s):  
Cornel J. M. Kerkhof ◽  
Erik N. T. P. Bakker ◽  
Pieter Sipkema
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
No Production ◽  
Cremaster Muscle ◽  
Resistance Arteries ◽  
Arterial Diameter ◽  
Spontaneous Tone ◽  
Cytochrome P 450

The role of arachidonic acid metabolism and nitric oxide (NO) in hypoxia-induced changes of vascular tone was investigated in first-order cannulated rat cremaster muscle resistance arteries. Spontaneous tone reduced arterial diameter from 179 ± 2 μm (fully dilated) to 98 ± 3 μm under normoxia ([Formula: see text] = 150 mmHg). Hypoxia ([Formula: see text] 5–10 mmHg) had no significant effect on arterial diameter under conditions of spontaneous tone. The effect of hypoxia was not changed after blockade of cyclooxygenase with indomethacin or after blockade of lipoxygenase with nordihydroguaiaretic acid. However, after partial blockade of cytochrome P-450 4A enzymes with 17-octadecynoic acid (17-ODYA), hypoxia increased the diameter by 65 ± 6 μm ( P < 0.05). This increase could be inhibited by N G-nitro-l-arginine (l-NNA) or 20-hydroxyeicosatetraenoic acid (20-HETE). 17-ODYA induced a concentration-dependent dilation under normoxia, which could be blocked by endothelium removal orl-NNA. 17-ODYA did not increase smooth muscle sensitivity to NO. We conclude that, under conditions of spontaneous tone and in the absence of luminal flow, hypoxia (5–10 mmHg) has no effect on the diameter of resistance arteries from the rat cremaster muscle. Inhibition of the cytochrome P-450 4A pathway of arachidonic acid metabolism under normoxia induces NO production by the endothelium. Hypoxia induces an NO-mediated dilation when cytochrome P-450 4A enzymes are partially inhibited.

scholarly journals Glycemic control prevents microvascular remodeling and increased tone in Type 2 diabetes: link to endothelin-1

2009 ◽  
Vol 296 (4) ◽  
pp. R952-R959 ◽  
Author(s):  
Kamakshi Sachidanandam ◽  
Jim R. Hutchinson ◽  
Mostafa M. Elgebaly ◽  
Erin M. Mezzetti ◽  
Anne M. Dorrance ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Receptor Expression ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Gk Rats ◽  
Endothelin 1 ◽  
Vascular Compliance

Medial thickening and vascular hypertrophy of resistance arteries can lead to cardiovascular complications associated with diabetes. While previous studies have established a role of Type 1 diabetes in vascular remodeling, we recently extended these observations to Type 2 diabetes and reported increased collagen deposition due to alterations in matrix metalloproteinase expression and activity in mesenteric resistance arteries. These studies also showed that remodeling response was mediated by endothelin-1 (ET-1) via activation of ETA receptors, whereas blockade of ETB receptors exacerbated the remodeling. However, the effectiveness of glycemic control strategies in preventing these vascular changes, including activation of the ET system still remained unclear. Also, very little is known about whether and to what extent reorganization of the extracellular matrix (ECM) affects vascular compliance and vasomotor tone. Accordingly, this study assessed structural remodeling of mesenteric microvessels, vascular compliance, and myogenic tone, as well as the role of matrix metalloproteinases (MMP) in mediating these processes. Spontaneously diabetic, non-obese Goto-Kakizaki (GK) rats, a model for Type 2 diabetes, and normoglycemic Wistar rats were used for the studies. A subset of GK rats were administered metformin to achieve euglycemia. Glycemic control normalized the increased media-to-lumen ratios (M/L) and myogenic tone seen in diabetes, as well as normalizing plasma ET-1 levels and mesenteric ETA receptor expression. There was increased collagen synthesis in diabetes paralleled by decreased collagenase MMP-13 activity, while glycemic control attenuated the process. These findings and our previous study taken together suggest that hyperglycemia-mediated activation of ET-1 and ETA receptors alter vascular structure and mechanics in Type 2 diabetes.

Remodeling of resistance arteries in organoid culture is modulated by pressure and pressure pulsation and depends on vasomotion

2004 ◽  
Vol 286 (6) ◽  
pp. H2052-H2056 ◽  
Author(s):  
Erik N. T. P. Bakker ◽  
Oana Sorop ◽  
Jos A. E. Spaan ◽  
Ed VanBavel
Keyword(s):  
High Pressure ◽  
Vascular Remodeling ◽  
Pressure Pulsation ◽  
Progressive Increase ◽  
Pressure Level ◽  
Lumen Diameter ◽  
Myogenic Tone ◽  
Cremaster Muscle ◽  
Resistance Arteries ◽  
Organoid Culture

The hypothesis was tested that pressure and pressure pulsation modulate vascular remodeling. Arterioles (∼200 μm lumen diameter) were dissected from rat cremaster muscle and studied in organoid culture. In the first series, arterioles were kept at a stable pressure level of either 50 or 100 mmHg for 3 days. Both groups showed a progressive increase in myogenic tone during the experiment. Arterioles kept at 50 mmHg showed larger endothelium-dependent dilation, compared with vessels kept at 100 mmHg on day 3. Remodeling, as indicated by the reduction in maximally dilated diameter at 100 mmHg, was larger in arterioles kept at 50 mmHg compared with 100 mmHg: 34 ± 4.5 versus 10 ± 4.8 μm ( P < 0.05). In the second series, arterioles were subjected to a stable pressure of 60 mmHg or oscillating pressure of 60 ± 10 mmHg (1.5 Hz) for 4 days. Pressure pulsation induced partial dilation and was associated with less remodeling: 34 ± 4.0 versus 19 ± 4.5 μm ( P < 0.01) for stable pressure versus oscillating pressure. Vasomotion was frequently observed in all groups, and inward remodeling was larger in vessels with vasomotion: 30 ± 2.5 μm compared with vessels that did not exhibit vasomotion: 8.0 ± 5.0 μm ( P < 0.01). In conclusion, these results indicate that remodeling is not enhanced by high pressure. Pressure pulsation causes partial dilation and reduces inward remodeling. The appearance of vasomotion is associated with enhanced inward remodeling.

Monitoring the marine environment for small round structured viruses (SRSVS): a new approach to combating the transmission of these viruses by molluscan shellfish

1998 ◽  
Vol 38 (12) ◽  
pp. 51-56 ◽  
Author(s):  
K. Henshilwood ◽  
J. Green ◽  
D. N. Lees
Keyword(s):  
Enteric Virus ◽  
Winter Period ◽  
Rt Pcr ◽  
Cloning And Sequencing ◽  
New Approach ◽  
Human Enteric Virus ◽  
Different Strains ◽  
The Uk ◽  
Public Health Protection

This study investigates human enteric virus contamination of a shellfish harvesting area. Samples were analysed over a 14-month period for Small Round Structured Viruses (SRSVs) using a previously developed nested RT-PCR. A clear seasonal difference was observed with the largest numbers of positive samples obtained during the winter period (October to March). This data concurs with the known winter association of gastroenteric illness due to oyster consumption in the UK and also with the majority of the outbreaks associated with shellfish harvested from this area during the study period. RT-PCR positive amplicons were further characterised by cloning and sequencing. Sequence analysis of the positive samples identified eleven SRSV strains, of both Genogroup I and Genogroup II, occurring throughout the study period. Many shellfish samples contained a mixture of strains with a few samples containing up to three different strains with both Genogroups represented. The observed common occurrence of strain mixtures may have implications for the role of shellfish as a vector for dissemination of SRSV strains. These results show that nested RT-PCR can identify SRSV contamination in shellfish harvesting areas. Virus monitoring of shellfish harvesting areas by specialist laboratories using RT-PCR is a possible approach to combating the transmission of SRSVs by molluscan shellfish and could potentially offer significantly enhanced levels of public health protection.

scholarly journals Spontaneous Retroperitoneal Hematoma in COVID-19 Severe Pneumonia–Dual-phase Multidetector Computed Tomography (MDCT) Angiogram and Role of Radiologist

2021 ◽  
Author(s):  
Vikash Kumar Gupta ◽  
Buthaina Mohammad Alkandari ◽  
Wasif Mohammed ◽  
Mohsen Ahmed Abdelmohsen ◽  
Mohammad Gaber Abdullah Mohammad
Keyword(s):  
Significant Risk ◽  
Severe Pneumonia ◽  
Retroperitoneal Hematoma ◽  
Low Molecular Weight ◽  
Rt Pcr ◽  
Prophylactic Dose ◽  
Therapeutic Anticoagulation ◽  
Coagulation Tests ◽  
Polymerase Chain

AbstractStudies available in the literature have shown alterations in blood coagulation tests in severe cases of COVID-19 pneumonia, with a significant risk of venous thromboembolism (VTE). Since microvascular thrombosis is a well-known fact in COVID-19 disease, requiring therapeutic anticoagulation, low-molecular weight heparin (LMWH) in prophylactic dose is a part of the clinical management of hospitalized COVID-19 patients. In this scenario, we describe three cases of abdominal spontaneous retroperitoneal hematoma (SRH) in hospitalized reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients.

scholarly journals The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-β pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuanfeng Gao ◽  
Ye Liu ◽  
Yuan Fu ◽  
Qianhui Wang ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Expression Patterns ◽  
In Silico Analysis ◽  
Significant Negative Correlation ◽  
Circular Rnas ◽  
Tgf Beta ◽  
Rt Pcr ◽  
Derivation Cohort ◽  
Tgf Β1

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = − 0.797, p < 0.001). Conclusion CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

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