CALCIUM DOBESILATE INCREASES ENDOTHELIUM-DEPENDENT RELAXATION IN ENDOTHELIUM-INJURED RABBIT AORTA

1998 ◽  
Vol 38 (5) ◽  
pp. 361-366 ◽  
Author(s):  
EMILIO RUIZ ◽  
TERESA TEJERINA
1994 ◽  
Vol 266 (2) ◽  
pp. H590-H596 ◽  
Author(s):  
I. R. Hutcheson ◽  
T. M. Griffith

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.


1984 ◽  
Vol 21 (5) ◽  
pp. 223-230 ◽  
Author(s):  
Harold A. Singer ◽  
Jo Anne Saye ◽  
Micheal J. Peach

1989 ◽  
Vol 67 (11) ◽  
pp. 1454-1460 ◽  
Author(s):  
Laal Jayakody ◽  
Manohara P. J. Senaratne ◽  
Alan B. R. Thomson ◽  
Nadarajan Sreeharan ◽  
C. Tissa Kappagoda

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.


1993 ◽  
Vol 21 (6) ◽  
pp. 893-901 ◽  
Author(s):  
Bernd C. Simon ◽  
Christian C. Haudenschild ◽  
Richard A. Cohen ◽  
James Palacino

1985 ◽  
Vol 63 (9) ◽  
pp. 1206-1209 ◽  
Author(s):  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda

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.


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

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.


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