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Alterations of the endothelial function of isolated aortae in rats with adjuvant arthritis.

Adjuvant arthritis was induced in 30 male Wistar rats by injection into the tail of heat-killed Mycobacterium butyricum. Three weeks later, 14 of these rats exhibited severe arthritic lesions. Their thoracic aortae were studied in parallel with those isolated from a control group. On rings precontracted with phenylephrine (0.1 microM), the endothelium-dependent relaxations produced by acetylcholine and histamine were significantly diminished in the arthritic group as compared to the control group. Moreover, the increase in tone induced by incubation with methylene blue (10 microM) (a nonspecific inhibitor of endothelium-derived relaxing factor) was significantly less pronounced in preparations isolated from the arthritic group. On the other hand, relaxations produced by the endothelium-independent vasodilators verapamil and nitroprusside were similar in both groups. It is concluded that adjuvant arthritis modifies the endothelium-derived relaxing factor-mediated responses of rat aorta.

Acetylcholine

Decreased endothelial pump function with aging.

Endothelial function may be affected by the endothelial cell loss and increased variability in cell shape and size (polymegathism) that accompany normal aging. Endothelial function can be evaluated by monitoring corneal hydration recovery following hypoxic stress. The authors compared corneal recovery and endothelial morphology between a group of younger (mean = 26.7 yr) and older (means = 65.7 yr) subjects with normal corneas. Edema (60 microns) was induced with hydrogel lenses worn with the eyes closed. Following lens removal, the decrease in corneal thickness was monitored for 4 hr with one eye open while the contralateral eye remained closed. For both age groups, corneal recovery followed a non-linear time course. The open eye required 2.5 hr and 3.0 hr to return to baseline for the younger and older age groups, respectively. Recovery during eye closure took 3.5 hr to reach the normal closed eye level for the younger subjects and was not complete at 4 hr for the older subjects. Recovery rates were significantly slower for the older vs younger subjects during the first 2 hr of closed eye recovery, 10.5 vs 15.0 microns/hr, and for the initial 1 hr of open eye recovery, 26.5 vs 35.6 microns/hr. For both age groups combined, the rate of recovery was negatively correlated with the coefficient of variation in cell area, r = -0.62 and -0.69 (P less than 0.01), for both closed and open eye recovery, respectively. When each morphological characteristic was isolated, the only significant correlation found was between the coefficient of variation in cell area and the rate of recovery during eye closure, r = -0.66 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Modulation of membrane cholesterol levels: effects on endothelial cell function.

The endothelial cell lining of blood vessels is now recognized as an active interface between blood and the underlying tissue. Modulation of cholesterol levels in several cell types has resulted in altered cell function. We have removed cholesterol from the endothelial cell membrane and have observed corresponding alterations in endothelial cell function. Following depletion of cholesterol from the endothelial cells, polymorphonuclear leukocyte adhesion to the cells was decreased. Angiotensin-converting enzyme activity of the endothelial cells was increased following removal of cholesterol from the endothelial cell membranes. The results of fluorescence polarization measurements suggest that these changes may be partially explained by altered membrane order.

Animals

Detrimental effects of temperature on the efficacy of the University of Wisconsin solution when used for cardioplegia at moderate hypothermia. Comparison with the St. Thomas Hospital solution at 4 degrees C and 20 degrees C.

BACKGROUND: We have previously reported the superior protective properties of the University of Wisconsin (UW) solution compared with the St. Thomas solution (ST) in the rat heart subjected to the deep hypothermia (4 degrees C), thus demonstrating its possible use in cardiac transplantation. We thought it was important to evaluate the potential of the UW solution as a cardioplegic solution under the moderately hypothermic (20 degrees C) conditions of routine intraoperative myocardial protection. METHODS AND RESULTS: Isolated rat hearts were subjected to 60 minutes of ischemia at 4 degrees C or 30 (or 60) minutes of ischemia at 20 degrees C with UW, ST, and ST plus 100 mM K (ST + 100) solutions. Coronary flow, mechanical function, endothelial function, and ultrastructure were observed. Mean time (seconds) to infuse 10 ml of cardioplegic solution under constant pressure, a measure of coronary vascular resistance at 4 degrees C and 20 degrees C, respectively, for each solution were ST, 69.2 +/- 6.9 and 64.7 +/- 3.8; UW, 142.2 +/- 8.8 and 187.2 +/- 10.0 (p < 0.01); and ST + 100, 78.2 +/- 8.0 and 176 +/- 8.1 (p < 0.001). Mean recovery values of cardiac output (expressed as percentage of its preischemic value) after 60 minutes of ischemia at 4 degrees C were ST, 95.5 +/- 2.1%; UW, 93.0 +/- 2.4%; and ST + 100, 96.5 +/- 1.5%. After 30 minutes of ischemia at 20 degrees C, values were ST, 88.0 +/- 1.3%; UW, 72.2 +/- 3.6% (p < 0.005 versus ST); and ST + 100, 53.3 +/- 1.8% (p < 0.001 versus ST). CONCLUSIONS: The efficacies of UW and severely hyperkalemic cardioplegic solutions are affected by the degree of hypothermia under which they are used. Under moderate hypothermia (20 degrees C), severe hyperkalemia induces a marked increase in coronary vascular resistance that is associated with impaired myocardial protection. These studies discourage the use of UW for routine intraoperative cardioplegic arrest where the degree of hypothermia cannot be readily controlled. The ST solution does not share this constraint.

Adenosine

Photodynamically induced alteration of cornea endothelial cell function.

Corneal endothelial cells were perfused in the specular microscope with varying concentrations of rose bengal. Corneas perfused with rose bengal in concentrations of 10(-6)M to 10(-5)M and exposed to light for periods of 0.5 to 5 min swelled at rates which were more rapid with both increasing concentration of rose bengal and increasing duration of light exposure. Corneas perfused with similar concentrations of rose bengal but not exposed to light did not swell. Combining rose bengal with 100 micrograms/ml superoxide dismutase did not reduce the corneal swelling following exposure to light, indicating that the photodynamically induced endothelial bengal perfusing solution eliminated corneal swelling following exposure of corneas to light. This indicates that the photodynamic effect of endothelium is secondary to cell functional alterations from the hydrogen peroxide produced during the dismutation reaction of superoxide free radical which is catalyzed by superoxide dismutase.

Animals

Endothelial barrier function.

The endothelial barrier in all organ beds allows the free exchange of water, but is restrictive to varying degrees to the transport of solutes such as albumin. For example, in the brain microvessels, the endothelial barrier restricts the transport of protein, whereas in fenestrated and continuous endothelial cells of the renal and lung endothelial cells, the endothelial barrier is semipermeable. The endothelial monolayer demonstrates selectivity, i.e., the permeation of molecules is inversely related to the molecular weight. Although the "pore" theory has been used to describe the transport across the endothelial barrier, the transport of solutes is also dependent on the charge of solutes and the endothelial cell, and the ability of the solute to bind to or be taken up by endothelial cells. Receptor-mediated trancytosis of albumin may contribute to albumin transport in addition to transport by paracellular pathways (i.e., through a so-called pore). Water permeability across the endothelium is determined by the interaction of albumin with glycocalyx and interstitial components of the endothelium (the "fiber matrix"). Ambient concentration of albumin serves to lower endothelial hydraulic conductivity. Increased endothelial permeability to solutes and water in inflammatory states is dependent on the shape and configuration of endothelial cells as determined by alterations in cytoskeletal elements, such as f-actin, and as regulated by intracellular second messengers such as free cytosolic calcium.

Animals