EFFECTS OF CONTRACTILE STIMULI ON EXCHANGES OF ELECTROLYTES BETWEEN UTERINE TISSUES AND A SALINE–BICARBONATE MEDIUM

1959 ◽  
Vol 37 (1) ◽  
pp. 127-148 ◽  
Author(s):  
Edwin E. Daniel ◽  
Betty N. Daniel

(1) Evidence has been presented suggesting that progesterone pretreatment in vivo increases the rate of leakage of potassium from rabbit uterine segments into a saline–bicarbonate medium.(2) Various types of evidence indicate that in uterine tissues, the loss of potassium from cells into potassium-free solutions is increased during the contractile actions of drugs. There was no clear-cut concomitant increase in tissue sodium concentrations. The results tend to confirm previous findings indicating that increases in potassium (but not in sodium) permeability are associated with contraction of smooth muscle.(3) Epinephrine effects on potassium loss occurred only in uteri which contracted in response to epinephrine. Norepinephrine, but not iproterenol, had a similar effect. Dibenamine, alone, decreased potassium loss and partly blocked the effects of epinephrine. Direct measurement of glycogen content suggested that these findings were not related to a glycogenolytic action of the epinephrine. Rather, the effect of epinephrine to increase potassium loss seemed to be closely related to its contractile action. In long-term experiments, both epinephrine and calcium slowed the rate of K loss and of water and sodium gain. This effect also was absent in uterine tissues which were not contracted by epinephrine.

1959 ◽  
Vol 37 (1) ◽  
pp. 127-148
Author(s):  
Edwin E. Daniel ◽  
Betty N. Daniel

(1) Evidence has been presented suggesting that progesterone pretreatment in vivo increases the rate of leakage of potassium from rabbit uterine segments into a saline–bicarbonate medium.(2) Various types of evidence indicate that in uterine tissues, the loss of potassium from cells into potassium-free solutions is increased during the contractile actions of drugs. There was no clear-cut concomitant increase in tissue sodium concentrations. The results tend to confirm previous findings indicating that increases in potassium (but not in sodium) permeability are associated with contraction of smooth muscle.(3) Epinephrine effects on potassium loss occurred only in uteri which contracted in response to epinephrine. Norepinephrine, but not iproterenol, had a similar effect. Dibenamine, alone, decreased potassium loss and partly blocked the effects of epinephrine. Direct measurement of glycogen content suggested that these findings were not related to a glycogenolytic action of the epinephrine. Rather, the effect of epinephrine to increase potassium loss seemed to be closely related to its contractile action. In long-term experiments, both epinephrine and calcium slowed the rate of K loss and of water and sodium gain. This effect also was absent in uterine tissues which were not contracted by epinephrine.


Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 66-76 ◽  
Author(s):  
MC Galmiche ◽  
VE Koteliansky ◽  
J Briere ◽  
P Herve ◽  
P Charbord

In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle- specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha- SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype.


2019 ◽  
Vol 68 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Annele Sainio ◽  
Piia Takabe ◽  
Sanna Oikari ◽  
Henriikka Salomäki-Myftari ◽  
Markku Koulu ◽  
...  

Metformin is the first-line drug in the treatment of type 2 diabetes worldwide based on its effectiveness and cardiovascular safety. Currently metformin is increasingly used during pregnancy in women with gestational diabetes mellitus, even if the long-term effects of metformin on offspring are not exactly known. We have previously shown that high glucose concentration increases hyaluronan (HA) production of cultured human vascular smooth muscle cells (VSMC) via stimulating the expression of hyaluronan synthase 2 (HAS2). This offers a potential mechanism whereby hyperglycemia leads to vascular macroangiopathy. In this study, we examined whether gestational metformin use affects HA content in the aortic wall of mouse offspring in vivo. We also examined the effect of metformin on HA synthesis by cultured human VSMCs in vitro. We found that gestational metformin use significantly decreased HA content in the intima-media of mouse offspring aortas. In accordance with this, the synthesis of HA by VSMCs was also significantly decreased in response to treatment with metformin. This decrease in HA synthesis was shown to be due to the reduction of both the expression of HAS2 and the amount of HAS substrates, particularly UDP-N-acetylglucosamine. As shown here, gestational metformin use is capable to program reduced HA content in the vascular wall of the offspring strongly supporting the idea, that metformin possesses long-term vasculoprotective effects.


2003 ◽  
Vol 95 (1) ◽  
pp. 448-453 ◽  
Author(s):  
Jahanbakhsh Naghshin ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow

It has been shown that airway smooth muscle in vitro is able to maintain active force over a large length range by adaptation in the absence of periodic stimulations at 4°C (Wang L, Paré PD, and Seow CY. J Appl Physiol 90: 734–740, 2001). In this study, we show that such adaptation also takes place at body temperature and that long-term adaptation results in irreversible functional change in the muscle that could lead to airway hyperresponsiveness. Rabbit tracheal muscle explants were passively maintained at shortened and in situ length for 3 and 7–8 days in culture media; the length-tension relationship was then examined. The length associated with maximal force generation decreased by 10.5 ± 3.8% (SE) after 3 days and 37.7 ± 8.5% after 7 or 8 days of passive shortening. At day 3, the left shift in the length-tension curve due to adaptation at short lengths was reversible by readapting the muscle at a longer length. The shift was, however, not completely reversible after 7 days. The results suggest that long-term adaptation of airway smooth muscle could lead to increased muscle stiffness and force-generating ability at short lengths. Under in vivo condition, this could translate into resistance to stretch-induced relaxation and excessive airway narrowing.


1979 ◽  
Vol 18 (1) ◽  
pp. 18-32 ◽  
Author(s):  
G.S. Dimitrievich ◽  
K. Fischer-Dzoga ◽  
R.M. Lee ◽  
M.L. Griem

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 888-893 ◽  
Author(s):  
Daniel V. Lejnieks ◽  
N. Ramesh ◽  
Stella Lau ◽  
William R.A. Osborne

Abstract To approach the goal of consistent long-term erythropoietin (Epo) expression in vivo, we developed an implantation procedure in which transduced autologous vascular smooth muscle was introduced into rats in a chamber created from a polytetrafluoroethylene (PTFE) ring placed under the serosa of the stomach. The implant became vascularized and permitted the long-term survival of smooth muscle cells expressing Epo. Hematocrits of treated animals increased rapidly and monitored over 12 months gave a mean value of 56.0 ± 4.0% (P < .001; n = 9), increased from a presurgery mean of 42.3 ± 1.6%. Hemoglobin levels rose from a presurgery mean of 15.2 ± 0.4 g/dL and for 12 months were significantly elevated with a mean value of 19.5 ± 1.3 g/dL (P < .001; n = 9). The hematocrit and hemoglobin levels of control animals receiving human adenosine deaminase (ADA)–expressing cells were not significantly different from baseline (P > .05; n = 5). In response to tissue oxygenation, kidney, and (to a lesser extent) liver are specific organs that synthesize Epo. Treated animals showed downregulation of endogenous Epo mRNA in kidney over a 12-month period. The PTFE implant provides sustained gene delivery, is safe, and is minimally invasive. It allows easy engraftment of transduced cells and may be applied generally to the systemic delivery of therapeutic proteins such as hormones and clotting factors. © 1998 by The American Society of Hematology.


1985 ◽  
Vol 107 (3) ◽  
pp. R9-R12 ◽  
Author(s):  
A. T. Holder ◽  
R. Aston ◽  
M.A. Preece ◽  
J. Ivanyi

ABSTRACT This work demonstrates that complexing hGH with monoclonal antibody EBl (MAB-EBl) can produce a striking potentiation of the somatogenic actions of hGH in vivo in Snell dwarf mice. In short-term experiments significant increases in cartilage metabolism and body weight were noted; these responses were dose-dependent for both MAB-EBl and hGH concentration. Increased growth was also observed in long-term experiments. In marmosets where MAB-EBl cross-reacts with endogenous GH, MAB-EBl alone enhanced the actions of endogenous GH. A new perspective may be necessary to incorporate these results into the current concept of antibody action.


Author(s):  
David C. Adams ◽  
Jasmin A. Holz ◽  
Margit V. Szabari ◽  
Lida P. Hariri ◽  
Andrew F. Mccrossan ◽  
...  

The inability to assess and measure changes to the airway smooth muscle (ASM) in vivo is a major challenge to evaluating asthma and its clinical outcomes. Bronchial thermoplasty (BT) is a therapy for asthma that aims to reduce the severity of excessive bronchoconstriction by ablating ASM. While multiple long-term clinical studies of BT have produced encouraging results, the outcomes of BT treatment in practice have been variable, and questions remain regarding the selection of patients. Previously we have demonstrated an imaging platform called orientation-resolved optical coherence tomography that can assess ASM endoscopically using an imaging catheter compatible with bronchoscopy. In this work, we present results obtained from a longitudinal BT study performed using a canine model (n = 8) and with the goal of investigating the use of OR-OCT for measuring the effects of BT on ASM. We demonstrate that we are capable of accurately assessing ASM both before and in the weeks following the BT procedure using blinded matching to histological samples stained with Masson's Trichome (p < 0.0001, r2 = 0.79). Analysis of volumetric ASM distributions revealed significant decreases in ASM in treated airways (average cross-sectional ASM area: 0.245 ± 0.145 mm2 pre-BT and 0.166 ± 0.112 mm2 6 weeks following BT). These results demonstrate that OR-OCT can provide clinicians with the feedback necessary to better evaluate ASM and its response to BT, and may potentially play an important role in phenotyping asthma and predicting which patients are most likely to respond to BT treatment.


Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 888-893 ◽  
Author(s):  
Daniel V. Lejnieks ◽  
N. Ramesh ◽  
Stella Lau ◽  
William R.A. Osborne

To approach the goal of consistent long-term erythropoietin (Epo) expression in vivo, we developed an implantation procedure in which transduced autologous vascular smooth muscle was introduced into rats in a chamber created from a polytetrafluoroethylene (PTFE) ring placed under the serosa of the stomach. The implant became vascularized and permitted the long-term survival of smooth muscle cells expressing Epo. Hematocrits of treated animals increased rapidly and monitored over 12 months gave a mean value of 56.0 ± 4.0% (P < .001; n = 9), increased from a presurgery mean of 42.3 ± 1.6%. Hemoglobin levels rose from a presurgery mean of 15.2 ± 0.4 g/dL and for 12 months were significantly elevated with a mean value of 19.5 ± 1.3 g/dL (P < .001; n = 9). The hematocrit and hemoglobin levels of control animals receiving human adenosine deaminase (ADA)–expressing cells were not significantly different from baseline (P > .05; n = 5). In response to tissue oxygenation, kidney, and (to a lesser extent) liver are specific organs that synthesize Epo. Treated animals showed downregulation of endogenous Epo mRNA in kidney over a 12-month period. The PTFE implant provides sustained gene delivery, is safe, and is minimally invasive. It allows easy engraftment of transduced cells and may be applied generally to the systemic delivery of therapeutic proteins such as hormones and clotting factors. © 1998 by The American Society of Hematology.


2020 ◽  
Vol 40 (5) ◽  
pp. 1068-1077
Author(s):  
Mark Butlin ◽  
Isabella Tan ◽  
Bart Spronck ◽  
Alberto P. Avolio

The arterial wall is a composite material of elastin, collagen, and extracellular matrix with acutely modifiable material properties through the action of smooth muscle cells. Therefore, arterial stiffness is a complex parameter that changes not only with long-term remodeling of the wall constituents but also with acute contraction or relaxation of smooth muscle or with changes in the acute distending pressure to which the artery is exposed. It is not possible to test all these aspects using noninvasive or even invasive techniques in humans. Full characterization of the mechanical properties of the artery and the specific arterial factors causing changes to stiffness with disease or modified lifestyle currently require animal studies. This article summarizes the major in vivo and ex vivo techniques to measure the different aspects of arterial stiffness in animal studies.


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