Persistent impairment of endothelium-dependent relaxation to acetylcholine and progression of atherosclerosis following 6 weeks of cholesterol feeding in the rabbit

1989 ◽  
Vol 67 (11) ◽  
pp. 1454-1460 ◽  
Author(s):  
Laal Jayakody ◽  
Manohara P. J. Senaratne ◽  
Alan B. R. Thomson ◽  
Nadarajan Sreeharan ◽  
C. Tissa Kappagoda
Keyword(s):  
Rabbit Aorta ◽  
Atherogenic Diet ◽  
Acute Stage ◽  
Standard Laboratory ◽  
Cholesterol Feeding ◽  
Functional Abnormality ◽  
New Zealand White Rabbits ◽  
Standard Laboratory Diet ◽  
Endothelium Dependent Relaxation ◽  
Progression Of Atherosclerosis

The synthesis and (or) release of endothelium-dependent relaxant factor released by acetylcholine is impaired in New Zealand white rabbits fed an atherogenic diet. Experiments were designed to investigate whether the synthesis and (or) release of the endothelium-dependent relaxant factor from rabbit aortas are restored after reversal from an atherogenic diet to a non-atherogenic diet. Atherosclerosis was induced by feeding a diet containing lipids and 2% cholesterol for 6 weeks. Rabbits were sacrificed after 6 weeks on the atherogenic diet and 36 weeks after return to a standard laboratory diet. Synthesis and (or) release of the factor from the thoracic aorta was assayed using a bioassay system. The relaxant responses produced in the assay tissue were impaired both in the acute stage and after 36 weeks on non-atherogenic food. This impaired relaxation is probably due to a persistent functional abnormality in the aortic endothelium resulting in the failure to synthesize and (or) release endothelium-dependent relaxation factor 36 weeks after induction of atherosclerosis.Key words: endothelium dependent relaxation, rabbit aorta, atherosclerosis, regression, cholesterol feeding.

Cholesterol feeding impairs endothelium-dependent relaxation of rabbit aorta

1985 ◽  
Vol 63 (9) ◽  
pp. 1206-1209 ◽  
Author(s):  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda
Keyword(s):  
New Zealand ◽  
Thoracic Aorta ◽  
Rabbit Aorta ◽  
Cholesterol Diet ◽  
Cholesterol Feeding ◽  
New Zealand White Rabbits ◽  
Conventional Diet ◽  
Endothelium Dependent Relaxation

Experiments were designed to assess the effect of cholesterol feeding on the endothelium-mediated relaxation of the rabbit aorta to acetylcholine. Age-matched male New Zealand white rabbits were fed either a 2% cholesterol diet or standard rabbit chow. The animals were anaesthetized with sodium pentobarbitone and sacrificed after 4 and 8 weeks on these diets. Rings were prepared from the proximal thoracic aorta and examined in tissue baths. These rings were contracted first with norepinephrine (−6 log mol/L) and acetylcholine was added to demonstrate the endothelium-mediated relaxation. The endothelium-dependent relaxation was significantly less in aortas from rabbits fed the 2% cholesterol diet than in aortas from animals fed the conventional diet. This impairment of relaxation was apparent after both 4 and 8 weeks of cholesterol feeding. In both groups of animals no relaxation was seen in rings from which the endothelium was removed. These results show that cholesterol feeding leads to an impairment of endothelium-mediated relaxation of the rabbit aorta to acetylcholine.

A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit

1990 ◽  
Vol 68 (7) ◽  
pp. 845-850 ◽  
Author(s):  
C. Tissa Kappagoda ◽  
Alan B. R. Thomson ◽  
Manohara P. J. Senaratne
Keyword(s):  
Rabbit Model ◽  
Rabbit Aorta ◽  
Control Group ◽  
Standard Diet ◽  
Cholesterol Feeding ◽  
High Cholesterol ◽  
Experimental Animals ◽  
New Zealand White Rabbits ◽  
Experimental Group ◽  
Endothelium Dependent Relaxation

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (−9.0 to −5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (−6.0 log mol/L) was significantly (p < 0.05) impaired in the experimental group (34.3 ± 3.8%) compared with that in the control group (79.8 ± 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 ± 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 ± 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.Key words: atherosclerosis, endothelium-dependent relaxation, rabbit aorta, regression.

Endothelium-dependent relaxation and experimental atherosclerosis in the rabbit aorta

1986 ◽  
Vol 64 (11) ◽  
pp. 1451-1453 ◽  
Author(s):  
N. Sreeharan ◽  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda
Keyword(s):  
Rabbit Aorta ◽  
Experimental Atherosclerosis ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Bicarbonate Buffer ◽  
New Zealand White Rabbits ◽  
Set Up ◽  
And Control ◽  
Dose Dependent ◽  
Endothelium Dependent Relaxation

This study was undertaken to determine whether the production or release of the endothelium-dependent relaxatory factor is impaired in atherosclerotic New Zealand White rabbits. Atherosclerosis was induced by feeding a diet containing 2% cholesterol for 6 weeks. The production or release of endothelium-dependent relaxatory factor was assayed as follows. A 5-cm length of aorta donor was perfused with Krebs–bicarbonate buffer and the perfusate drained over a deendothelialized ring of recipient aorta set up for recording isometric tension. The recipient was precontracted with norepinephrine (0.2 μmol/L) in the perfusate. When acetylcholine was added to the perfusate, the recipient relaxed in a dose-dependent manner. This assay was used to compare the relaxatory responses produced in recipient rings by adding acetylcholine to donors from atherosclerotic and control rabbits. The relaxation produced by atherosclerotic donors were smaller than those generated by control donors (16.5 ± 4.9 vs. 32.7 ± 5.3%; n = 10, p < 0.05). It is suggested that in atherosclerotic rabbits the ability of aortic endothelium to produce or release endothelium-dependent relaxatory factor is impaired.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

1975 ◽  
Vol 33 ◽  
pp. 460-461
Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks
Keyword(s):  
Lipid Metabolism ◽  
New Zealand ◽  
Aortic Wall ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Metabolic Changes ◽  
Atherosclerotic Plaques ◽  
Cytochemical Study ◽  
Cellular Alteration ◽  
New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

Plasma and white adipose tissue lipid composition in marmots

1990 ◽  
Vol 258 (5) ◽  
pp. R1123-R1131 ◽  
Author(s):  
G. L. Florant ◽  
L. C. Nuttle ◽  
D. E. Mullinex ◽  
D. A. Rintoul
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Plasma Free Fatty Acid ◽  
Laboratory Animals ◽  
Plasma Samples ◽  
Standard Laboratory ◽  
Marmota Flaviventris ◽  
Fa Composition ◽  
Omega 6 ◽  
Standard Laboratory Diet

White adipose tissue biopsies and plasma samples were obtained from hibernating yellow-bellied marmots (Marmota flaviventris) maintained in the laboratory. In addition, biopsies and plasma samples were obtained from normothermic animals in the field and laboratory. Measurement of plasma free fatty acid (FA) levels indicated that winter laboratory animals exhibited increased lipolysis. Additionally, analysis of white adipose tissue triacylglycerol revealed that the FA composition of the storage fat in animals maintained on the standard laboratory diet is remarkably simple and uniform between different adipose depots in the same animal. Three FAs (palmitic, oleic, and linoleic acids) made up greater than 95% of the total. Triene (alpha-linolenate) was found in newly captured animals, but the percentage of this FA decreased rapidly when the animals were maintained on the standard laboratory diet. Throughout the hibernation season (October to April), white adipose tissue-saturated FA percentage decreased, monoene percentage remained constant, and diene percentage increased. Analysis of plasma FA composition suggested that these animals tended to metabolize saturated FAs from stored lipid during hibernation and that dienes were mobilized briefly after the last arousal from hibernation in spring. From these observations, we hypothesize that marmots preferentially metabolize saturated fats during the hibernation period and that essential FAs of the omega 6 series tend to be metabolized more slowly than other FAs. These characteristics suggest that marmots are a valuable animal model in which to study lipid metabolism.

scholarly journals The Role of Bamboo Shoot Gigantochloa apus Extract in Decreasing MDA and Increasing IL-10 at The Atherosclerosis

2019 ◽  
Vol 3 (1) ◽  
pp. 23-27
Author(s):  
Edy Soesanto ◽  
Edi Dharmana ◽  
Soeharyo Hadisaputro ◽  
Siti Fatimah Muis
Keyword(s):  
Atherogenic Diet ◽  
Control Group ◽  
Antioxidant Compounds ◽  
Bamboo Shoot ◽  
Control Group Design ◽  
Treatment Groups ◽  
New Zealand White Rabbits ◽  
Post Test ◽  
Free Radical Formation

Introduction: Bamboo shoot Gigantochloa apus extract has antioxidant compounds that act as lipid peroxidation inhibitors and reduce free radical formation so that it can be used as an anti-inflammatory and anti-oxidative stress in the atherosclerosis. Aim: Knowing the effect of bamboo shoot Gigantochloa apus extract in reducing MDA levels and IL-10 increasing levels in rabbits given atherogenic diet. Methods: This experiment used randomized pre-test and post-test with control group design, in 24 New Zealand White rabbits divided into 4 groups randomly. MDA and IL-10 levels were examined by the ELISA method. Results and conclusion: Bamboo shoot Gigantochloa apus extract can reduce MDA levels and increase IL-10 levels significantly in accordance with increasing doses. The increase of MDA levels in the control group with all treatment groups was different (p = 0.0001), and between the treatment groups and other treatment groups there were also differences (p

Experimental cardiac necrosis in hypobaric and anemic hypoxia

1975 ◽  
Vol 39 (2) ◽  
pp. 205-208 ◽  
Author(s):  
J. J. McGrath ◽  
B. Ostadal ◽  
J. Prochazka ◽  
M. Wachtlova ◽  
V. Rychterova
Keyword(s):  
White Male ◽  
Male Rats ◽  
Standard Laboratory ◽  
Simulated Altitude ◽  
Subcutaneous Injections ◽  
The Third ◽  
Infant Rats ◽  
Significant Difference ◽  
Standard Laboratory Diet ◽  
Cardiac Necrosis

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.

Endothelium increases medial hydraulic conductance of aorta, possibly by release of EDRF

1993 ◽  
Vol 264 (1) ◽  
pp. H26-H32 ◽  
Author(s):  
A. L. Baldwin ◽  
L. M. Wilson
Keyword(s):  
Methyl Ester ◽  
Endothelial Permeability ◽  
Rabbit Aorta ◽  
Hydraulic Conductance ◽  
Control Value ◽  
New Zealand White Rabbits ◽  
Student’S T ◽  
Low Pressures ◽  
Student’S T Test

In eight anesthetized New Zealand White rabbits, the aorta was cannulated in situ for measurement of hydraulic conductance (Lp) at different pressures with and without endothelium. De-endothelialization increased Lp at > or = 75 mmHg but not at 50 mmHg. Because endothelium resists transmural water flow, the endothelium must also increase medial Lp at 50 mmHg. To determine whether this effect results from secretion of endothelial-derived relaxing factor (EDRF), Lp was measured in eight rabbits in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of EDRF synthesis. At 50 mmHg L-NAME reduced Lp from 6.79 +/- 2.19 to 2.59 +/- 1.41 (SD) x 10(-8) (P < 0.05, paired Student's t test). After L-NAME was removed, Lp returned to its control value. At 125 mmHg L-NAME did not significantly change Lp, although endothelial permeability seemed to increase. L-NAME did not affect Lp of nine de-endothelialized vessels at either pressure. An additional five experiments showed that the effect of L-NAME at 50 mmHg was reversed by L-arginine. Eleven additional experiments demonstrated that NG-nitro-D-arginine methyl ester does not affect Lp at 50 mmHg. These results indicate that EDRF increases Lp of the rabbit aorta at low pressures.

Heterogeneous populations of K+ channels mediate EDRF release to flow but not agonists in rabbit aorta

1994 ◽  
Vol 266 (2) ◽  
pp. H590-H596 ◽  
Author(s):  
I. R. Hutcheson ◽  
T. M. Griffith
Keyword(s):  
Shear Stress ◽  
Rabbit Aorta ◽  
Katp Channels ◽  
K Channel ◽  
K Channels ◽  
Kca Channels ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
High Conductance

We have investigated the role of Ca(2+)- and ATP-sensitive K+ channels (KCa and KATP, respectively) in flow- and agonist-stimulated release of endothelium-derived relaxing factor (EDRF). Segments of rabbit abdominal aorta, perfused at constant flow with buffer containing indomethacin, were used as a source of EDRF in cascade bioassay, and responses to endothelium-dependent agonists were studied isometrically in rings of the same tissue in the absence of flow. Apamin, charybdotoxin (ChTX), and tetraethylammonium (TEA) were used to block a variety of low, medium, and high conductance KCa channels, and glibenclamide was used to block KATP channels. The effects of flow pulsatility were studied at pulse frequencies ranging from 0.15 to 9.75 Hz, and time-averaged shear stress was manipulated by adding dextran (80,000 mol wt) to the perfusate to increase its viscosity. Frequency-related EDRF release was maximal at approximately 5 Hz and attenuated by apamin, TEA, and ChTX, but not by glibenclamide. EDRF release stimulated by increased viscosity was attenuated by TEA, ChTX, and glibenclamide, but not by apamin. In marked contrast, EDRF release stimulated by acetylcholine and ATP was unaffected by blockade of either KCa or KATP channels. We conclude that a spectrum of KCa channel subtypes mediates endothelial transduction of the oscillatory component of pulsatile flow and that KATP channels may be additionally involved in the transduction of time-averaged shear stress. In contrast, agonist-stimulated endothelium-dependent relaxation is independent of K+ channel activation in rabbit aorta.

Effects of Cytochrome P-450 Inhibitors on Endothelium-Dependent Relaxation in Rabbit Aorta

1984 ◽  
Vol 21 (5) ◽  
pp. 223-230 ◽  
Author(s):  
Harold A. Singer ◽  
Jo Anne Saye ◽  
Micheal J. Peach
Keyword(s):  
Rabbit Aorta ◽  
Cytochrome P 450 ◽  
Endothelium Dependent Relaxation
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