Chronic treatment of rats with D-600 causes a compensatory decrease in the calcium requirement for contractility of vascular smooth and cardiac muscles

1985 ◽  
Vol 63 (5) ◽  
pp. 495-499
Author(s):  
Catherine C. Y. Pang ◽  
Morley C. Sutter

We studied the effects of chronic hypotensive treatment of normotensive Wistar rats (NWR) with methoxyverapamil (D-600) and hydralazine on in vitro contractile response of aortic strips, portal vein strips, and Langendorff-perfused hearts in normal (2.5 mM) and low (0.2 mM) calcium (Ca). Portal vein strips from rats treated with D-600, compared with the same strips from control and hydralazine-treated rats, developed greater spontaneous contractile activity in normal Ca and retained greater responses to norepinephrine (NE) and 80 mM K in low Ca. Aortic strips from all three groups of rats retained similar responses to NE and K in low Ca. Hearts from D-600-treated rats produced less intraventricular pressure (IVP) to isoproterenol (ISO) than hearts from control and hydralazine-treated rats in normal Ca but greater IVP to ISO than hearts from the other two groups of rats in low Ca. Thus, chronic treatment of NWR with D-600 but not with hydralazine resulted in the reduction of Ca requirement for contractile activities of the portal vein and the myocardium.

1972 ◽  
Vol 50 (4) ◽  
pp. 289-299 ◽  
Author(s):  
G. A. Collins ◽  
M. C. Sutter ◽  
J. C. Teiser

Studies were done measuring contractile activity in the isolated rabbit anterior mesenteric–portal vein (A.M.V.). The rabbit A.M.V. requires external calcium for both spontaneous activity and the initiation and maintenance of contractions to agonists.After bathing the tissues in calcium-free Krebs' solution containing 1 mM ethyleneglycoltetraacetic acid (EGTA) for 10 min, and then washing out the EGTA, the re-addition of calcium produced a contraction. The pre-addition of a small amount of calcium (0.1 mM) after EGTA treatment (while not inducing a contractile response) alters subsequent contractile responses to larger concentrations of calcium. This is interpreted as the ability of membrane-bound calcium to control membrane permeability to calcium.Other experiments involved bathing the tissues in calcium-free solution until no response was obtained to agonists, and then re-adding calcium. The time course of the responses to noradrenaline after calcium re-addition depended on the length of calcium incubation. This suggests that noradrenaline can release a loosely bound calcium fraction which may be involved in controlling calcium influx. This bound calcium, however, does not provide a major source of activator calcium in normal Krebs' solution.


1989 ◽  
Vol 67 (10) ◽  
pp. 1272-1277 ◽  
Author(s):  
G. Pillai ◽  
M. C. Sutter

This study examines whether incubation with plasma from essential hypertensive patients increases the contractile activity of vascular smooth muscle from rats in response to noradrenaline (NA) and potassium (K+). Plasma samples were obtained from age- and sex-matched essential hypertensive patients and normotensive people. Vascular strips were prepared from aorta and portal veins of normotensive rats and placed in physiological solution in muscle baths for measurement of mechanical response. Aortic strips exposed to hypertensive plasma showed increased responsiveness to NA compared with normotensive plasma, but K+ caused an opposite effect. Portal vein exposed to normotensive or hypertensive plasma did not produce any response to NA, but the responsiveness produced in the presence of normotensive plasma to K+ was higher than that of hypertensive plasma. Portal vein exposed to normotensive plasma or hypertensive plasma showed a dose-dependent increase in the spontaneous activity up to 50% concentration of the plasma samples, but further increase in the concentration of plasma inhibited the spontaneous activity. Spontaneous activity at any given concentration of hypertensive plasma was significantly higher than that of normotensive plasma. The spontaneous activity in the presence of heated or unheated normotensive plasma or unheated normotensive serum was not significantly different from each other. These results indicate that the plasma factor from hypertensive patients, which alters the reactivity of vascular smooth muscle from normotensive rat, is present in the serum fraction and is not heat sensitive.Key words: hypertension, plasma, contractile response, circulating factor, spontaneous activity.


2019 ◽  
Vol 98 (9) ◽  
pp. 350-355

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.


2020 ◽  
Vol 6 (2) ◽  
pp. 155-169
Author(s):  
Neeraj Panihar ◽  
Neeru Vasudeva ◽  
Sunil Sharma ◽  
Babu Lal Jangir

Background: Fagopyrum esculentum Moench. is a herb consumed as food and has medicinal value. It is a rich source of bioactive nutrients which cure and prevent many ailments. Traditionally, it is used to treat hypertension, diabetes, constipation, cancer etc. Methods and Objective: Present work illustrates morphological, microscopic and physicochemical parameters of Fagopyrum esculentum seeds as per WHO guidelines, in vitro antioxidant activity; assessed by DPPH scavenging method, hydrogen peroxide scavenging assay and β-carotene linoleic acid bleaching method and study of lipid lowering potential of the ethyl acetate and ethanol extract of seeds on normal diet fed Wistar rats. Results: Morphological studies delineated the triangular shape, dark brown colour, 8 mm length and 6 mm width of the seed. The microscopic examination of the transverse section of seed depicted features like testa or pericarp (seed coat), the endosperm, embryo and sclerenchyma cells. Study of physiochemical parameters exhibited 0.3±0.02% of foreign matter and 1.44±0.51% crude fibre content. Total ash, acid insoluble ash and water soluble ash value were 6.7±1.7%, 1.9±0.23% and 3.9± 0.31% respectively. Alcohol soluble and water soluble extractive value came out to be 65.02± 3.21 mg/g and 12.7±1.24 mg/g respectively. Foaming index was less than 100, swelling index was found to be 0.5±0.01 ml/g. Loss on drying was 4.02±1.27%. Phytochemical screening of ethyl acetate and ethanol extract revealed the presence of alkaloids, carbohydrates, phenolic compounds, phytosterols and flavonoids. Trace amount of heavy metals (arsenic, cadmium, lead, mercury) were determined by atomic absorption spectrophotometer. Pesticide residue analysis confirmed the presence of nontoxic pesticides like dimethipin, hymexazol, phenothrin-2, methoprene, triadimenol, prohydrojasmon- 1, jasmolin ii, triademinol, jasmolin i, prohydrojasmone i, cyromazine in both the extracts by gc-ms spectrometer. The ethyl acetate and ethanol extract has shown significant in-vitro antioxidant activities demonstrated by the DPPH method (IC50 = 94.37±2.51 and 216.04±4.39 μg/ml respectively), hydrogen peroxide scavenging assay (IC50 = 83.72±3.72 and 193.47±5.05 µg/ml respectively) and β-carotene bleaching method (IC50 = 100.67±4.01 and 205.39±2.89 µg/ml respectively). Lipid lowering study performed on Wistar rats demonstrated a significant (p<0.001) decrease in serum Total Cholesterol (TC), Triglyceride (TG) and increase in High Density Lipoprotein (HDL) level as compared to normal group. Both the extracts have shown a non significant difference in the level of TG as compared to standard drug atorvastatin, depicting that the efficacy of extracts is at par with that of standard drug atorvastatin. Conclusion: Pharmacognostical study of the plant can be a very good tool for identification as well as authentication of a herb. Moreover, these parameters may be helpful in the development of monograph of the plant. Pharmacological activity confirmed Fagopyrum esculentum Moench. seed to be a good antioxidant and have lipid lowering potential.


1992 ◽  
Vol 20 (1) ◽  
pp. 71-76
Author(s):  
Andrea Trevisan ◽  
Stefano Maso ◽  
Paola Meneghetti

The in vitro renal cortical slice model was used to study: 1) the effects on the kidney of some haloalkanes and haloalkenes using 3-month-old male Wistar rats; 2) influence of age and sex on renal cortical slice indices in non-treated rats; and 3) effects of 1,2-dichloropropane on the slices after pretreatment of 3-month-old male Wistar rats with DL-butathionine-[S,R]-sulphoximine. The most nephrotoxic chemical used was 1,3-dichloropropene, which caused a total depletion in the levels of reduced glutathione, a high peroxidation of lipid (about three thousand-fold with respect to control), a significant release of tubular enzymes into the medium, and loss of organic anion ( p-aminohippurate) accumulation. All the chemicals affected the cytosol more than the brush border. The most remarkable age-related differences in the untreated slices were the progressive decrease of reduced glutathione (p<0.05 from three months of age), and an increase in lactate dehydrogenase release into the medium (p<0.05 from six months of age). By contrast, sex differences were slight. The ‘treatment with 1,2-dichloropropane of slices prepared from rats pretreated with DL-butathionine-[S,R]-sulphoximine significantly increased the depletion of glutathione content (p<0.05) and malondialdehyde release in the medium (p<0.001) caused by the solvent alone.


Author(s):  
Elvine P. Nguelefack-Mbuyo ◽  
Fernande P. Peyembouo ◽  
Christian K. Fofié ◽  
Télesphore B. Nguelefack

Abstract Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.


1999 ◽  
Vol 277 (1) ◽  
pp. H399-H404 ◽  
Author(s):  
Pilar Nava ◽  
Verónica Guarner ◽  
Rosalinda Posadas ◽  
Israel Pérez ◽  
Guadalupe Baños

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20–24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 μU/ml insulin resulted in increases in contractile responses: 41 ± 5.9 and 57 ± 6% for control and 65.5 ± 6 and 95 ± 9% for HTG aortas and femoral arteries, respectively. The endothelin ETB-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 ± 8 and 53 ± 5% in control and 48 ± 13 and 79 ± 3.5% in HTG aortas and femoral arteries, respectively. The ETA-receptor antagonist PD-151242 inhibited these responses by 12 ± 10 and 1 ± 9% in control and by 51.5 ± 9 and 58.5 ± 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.


2012 ◽  
Vol 302 (1) ◽  
pp. C141-C153 ◽  
Author(s):  
Susan G. Dorsey ◽  
Richard M. Lovering ◽  
Cynthia L. Renn ◽  
Carmen C. Leitch ◽  
Xinyue Liu ◽  
...  

Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB ( trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1 −/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function.


2002 ◽  
Vol 63 (12) ◽  
pp. 1687-1694 ◽  
Author(s):  
Marc Zulauf ◽  
Cecile Spring ◽  
Richard Eicher ◽  
Mireille Meylan ◽  
Gaby Hirsbrunner ◽  
...  
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