Role of wall tension in hypoxic responses of isolated rat pulmonary arteries

1998 ◽  
Vol 275 (6) ◽  
pp. L1069-L1077 ◽  
Author(s):  
Masami Ozaki ◽  
Carol Marshall ◽  
Yoshikiyo Amaki ◽  
Bryan E. Marshall
Keyword(s):  
Pulmonary Arteries ◽  
Mechanical Stretch ◽  
Effective Concentration ◽  
Active Tension ◽  
Wall Tension ◽  
Subsequent Response ◽  
Isolated Rat

The changes in force developed during 40-min exposures to hypoxia (37 ± 1 mmHg) were recorded in large (0.84 ± 0.02-mm-diameter) and small (0.39 ± 0.01-mm-diameter) intrapulmonary arteries during combinations of mechanical wall stretch tensions (passive + active myogenic components), equivalent to transmural vascular pressures of 5, 15, 30, 50, and 100 mmHg, and active (vasoconstriction) tensions, stimulated by PGF2α in doses of 0, 25, 50, and 75% effective concentrations. Constriction was observed in all arteries during the first minute; however, at any active tension, the pattern of the subsequent response was a function of the stretch tension. At 5, 15, and 30 mmHg, the constriction decreased slightly at 5 min and then increased again to remain constrictor throughout. At 50 and 100 mmHg, the initial constriction was followed by persistent dilation. Hypoxic constrictor responses, most resembling those observed in lungs in vivo and in vitro, were observed when the mechanical stretch wall tension was equivalent to 15 or 30 mmHg and the dose of PGF2α was 25 or 50% effective concentration. These observations reconcile many apparently contradictory results reported previously.

scholarly journals Piezo1 links mechanical forces to red blood cell volume

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stuart M Cahalan ◽  
Viktor Lukacs ◽  
Sanjeev S Ranade ◽  
Shu Chien ◽  
Michael Bandell ◽  
...  
Keyword(s):  
Blood Cell ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Conditional Knockout ◽  
Volume Control ◽  
Mechanical Forces ◽  
Gardos Channel

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.

Influence of mechanical stretch on growth and protein turnover of rat uterus

1988 ◽  
Vol 254 (5) ◽  
pp. E543-E548 ◽  
Author(s):  
A. J. Douglas ◽  
E. W. Clarke ◽  
D. F. Goldspink
Keyword(s):  
Mechanical Stretch ◽  
Rat Uterus ◽  
Dna Contents ◽  
Extensive Growth ◽  
A New Technique ◽  
Rna And Dna ◽  
Stimulation Of

A new technique has been developed and used to distend the uterus of nonpregnant rats for up to 5 days. Continuous distension of the saline-filled uterus induced rapid and extensive growth of the whole uterus and the myometrium by a combination of hyperplasia and hypertrophy. In both cases, 1 day after this imposition of mechanical stretch significant increases (25-50%) in the protein, RNA, and DNA contents were found, with larger changes (100-250%) being progressively expressed up to 5 days. This stretch-induced growth primarily results from a stimulation of protein synthesis (measured both in vivo and in vitro), with little or no change being evident in the rate of protein breakdown. These findings have been discussed in relation to the role of stretch in the growth of the uterus during pregnancy and stretch-induced responses found in other types of muscle.

Endothelin-receptor blockade does not alter closure of the ductus arteriosus

1998 ◽  
Vol 275 (5) ◽  
pp. H1620-H1626 ◽  
Author(s):  
Jeffrey R. Fineman ◽  
Yasushi Takahashi ◽  
Christine Roman ◽  
Ronald I. Clyman
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Receptor Blockade ◽  
Active Tension ◽  
In Vitro Effects ◽  
Ly 83583

Endothelin-1 (ET-1) is synthesized within the wall of the ductus arteriosus (DA) and is a potent constrictor of the DA in vitro. However, the role of endogenous ET-1 in closure of the DA at birth remains unclear. Therefore, we studied the effects of a selective ETA-receptor antagonist (PD-156707), or its vehicle, on DA closure in 13 late-gestation fetal lambs during the first 5 h after birth. We also studied the effects of ETA-receptor blockade on DA constriction induced by oxygen, indomethacin (a cyclooxygenase inhibitor), and LY-83583 (a soluble guanylate cyclase inhibitor) in vitro ( n = 9 ductus arteriosus rings). In vehicle-treated lambs in vivo, the DA constricted during the 5-h study period after birth: DA resistance increased (from 0.007 ± 0.01 to 3.406 ± 4.15 mmHg ⋅ ml−1 ⋅ min ⋅ kg−1; P < 0.05); the pressure gradient across the DA increased (from 1.4 ± 2.1 to 25.2 ± 9.4 mmHg; P < 0.05); and DA blood flow decreased (from 193.5 ± 48.0 to 19.3 ± 14.3 ml ⋅ kg−1 ⋅ min−1; P < 0.05). In vitro, the DA was constricted by exposure to 30% oxygen (23 ± 14% net active tension; P < 0.05), indomethacin (5 × 10−6 M, 22 ± 5% net active tension; P < 0.05), LY-83583 (10−5 M, 24 ± 10% net active tension; P < 0.05), and ET-1 (10−7 M, 19 ± 4% net active tension; P < 0.05). Although PD-156707 blocked both the in vivo and in vitro effects of exogenous ET-1, it had no effect on postnatal ductus constriction nor on in vitro ductus contractile responses to oxygen, indomethacin, or LY-83583. This study suggests that endogenous ET-1 does not play an important role in closure of the DA at birth.

Abstract 18: The Role of Matrix Metalloproteinase 12 in Vascular Stiffness, Inflammation and Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nataliya A Pidkovka ◽  
Jing Wu ◽  
Anna E Goldstein ◽  
Salim Thabet ◽  
David G Harrison
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Mechanical Stretch ◽  
Pressure Change ◽  
Vascular Stiffness ◽  
Western Blots ◽  
Expression And Activity

Vascular wall remodeling and inflammation contribute to hypertension. These processes decrease arterial elasticity due to a loss of elastin and deposition of collagen. Metalloproteinase-12 (MMP12) is an elastase produced by macrophages and vascular cells. Cleavage of elastin by MMP12 could increase vascular stiffness and lead to release of pro-inflammatory elastin fragments. We sought to determine if MMP12 contributes to hypertension and vascular stiffness in response to angiotensin II and to understand mechanisms responsible for its expression. To determine if mechanical stretch activates MMP12 we subjected cultured murine endothelial cells to 0%, 5% (normotensive) or 10% (hypertensive) uniaxial stretch for 48 hours. Real-time RT-PCR showed that 10% stretch increases MMP12 mRNA by 4 fold compared to 0% or 5% stretch. Western blots and casein zymography indicated that 10% stretch significantly increases MMP12 protein expression and activity, respectively. Western blots also revealed an increase in elastin fragments in the media of cells exposed to 10% stretch compared to those exposed to 5% stretch. To understand the role of MMP12 in hypertension, we infused angiotensin II in wild-type and MMP12 -/- mice. In keeping with the studies of cultured endothelial cells, angiotensin II markedly increased vascular MMP12 mRNA (10-fold) and protein levels. The hypertension caused by angiotensin II was markedly blunted in MMP12 -/- mice (122 ± 3 vs. 173 ± 5, p < 0.0001). Immunohistochemistry with a CD68 specific antibody indicated a significant decrease in macrophages accumulation in the perivascular tissues of MMP12 -/- compared to WT mice. We also examined distensibility of aortic segments in vitro, and quantified this as the percent change in diameter over a pressure change from 75 to 125 mmHg. Angiotensin II markedly decreased this distensibility index from 24 ± 3 to 9 ± 2%, but only to 16 ± 3% in MMP12 -/- mice (p < 0.05). In conclusion, these studies show that mechanical stretch in vitro and hypertension in vivo cause a striking increase in endothelial cell and vascular MMP12 expression and activity. MMP12 activation promotes aortic stiffening and ultimately hypertension. Thus, modulation of MMP12 might be a therapeutic target in hypertension.

scholarly journals The m6A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension via targeting PTEN

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Q I N Yuhan ◽  
T A N G Chengchun
Keyword(s):  
Pulmonary Arteries ◽  
Rna Modification ◽  
Funding Sources ◽  
Pten Mrna ◽  
Rna Immunoprecipitation ◽  
M6a Rna Methylation ◽  
And Migration

Abstract Background N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammal mRNAs. Accumulating evidence has indicated the crucial role of m6A modification in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, the role of m6A methylation in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. Purpose The present study aims to explore the role of key transferase METTL3, in the development of HPH. Methods Hypoxic rat models and pulmonary artery smooth muscle cells (PASMCs) and were used to research the METTL3-mediated m6A in HPH in vivo and in vitro. CCK-8, EdU, PCNA, transwell and TUNEL assay were performed to evaluate the proliferation, migration and apoptosis rates of PASMCs. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A-PTEN mRNA expression. RNA immunoprecipitation and RNA pull down were used to detect the interaction between METTL3 and PTEN mRNA. The half-life of mRNA was detected through actinomycin D assay. Results Both METTL3 mRNA and protein were found abnormally upregulated in pulmonary arteries of HPH rats and hypoxia induced PASMCs. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration exposed to hypoxia. In addition, m6A binding protein YTHDF2 was found significantly increased in HPH group in vivo and in vitro. Mechanistically, YTHDF2 recognized METTL3 mediated m6A-PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. Conclusion METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Natural Science Foundation of China Figure 1

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

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