Endothelial cell contractile protein

It is often possible to address function more specifically in in vitro assays, where functional parameters are usually very sensitive readouts of adverse effects. For example trans-epithelial electrical resistance (TEER) is a very sensitive marker of epithelial disturbances. TEER measures the barrier function of the entire mono-layer and is utilized to study functional disturbances of many epithelial/endothelial cell types including blood-brain barrier, pulmonary, renal, and gastrointestinal cells. Its sensitivity lies in the fact that only a small proportion of cell death has a very large impact on barrier function. Additionally, cell stress can interfere with the arrangement and population of tight junction proteins [16] thus, TEER can in certain conditions measure functional disturbances in the absence of cell death [13]. Also since TEER can be measured noninvasively, it is nondestructive and can be used to monitor the effects of treatment over days and weeks [13, 17]. For excitable cells, electrical activity has also been proven to be an extremely sensitive parameter of adverse drug reactions and microelectrode arrays have been employed successfully to monitor neurotoxicity in vitro [18]. Also, for contractile cells, such as cardiomyocytes, the use of impedance measurements to measure the effects of compounds on spontaneous contraction has been demonstrated to be a very sensitive functional monitoring parameter in vitro [19, 20], Admittedly, none of the aforementioned techniques are true biomarkers per se however, such measurements illustrate the fact that in vitro techniques allow certain possibilities that are not practically tenable in the whole body. 

Vernon SM, Campos MJ, Haystead T, Thompson MM, DiCorleto PE, Owens GK (1997) Endothelial cell-conditioned medium downregulates smooth muscle contractile protein expression. Am J Physiol 272(Cell Physiol 41) C582-C591... 

Endothelin-1 (ET-1) is a 21-amino-acid peptide that is produced by the vascular endothelium. It is a very potent vasoconstrictor that binds to VSM endothelin receptors ETa and ETB(Fig. 29.1). The ET-1 receptors are linked to the Gq protein and IP3 signal transduction pathway (Fig. 29.11). Therefore, ET-1 causes sarcoplasmic reticulum release of calcium, increasing the VSM contractility. Vascular endothelial cells secrete the majority of ET-1. The endothelins bind to two receptor subtypes ETa, and ETb. Invasculartissue, ETa is located predominantly on smooth muscle cells, whereas ETb is found on both endothelial and smooth muscle cells. Activation of ETa by ET-1 leads to potent vasoconstriction from an increase in cytosolic calcium levels via influx of extracellular calcium and release from intracellular stores (Fig. 29.1). The actions of ETb are more complicated. Like ETa, ET-1 activation of ETb on VSM cells leads to vasoconstriction. Furthermore, some studies suggest that in the pulmonary hypertensive state, blockade of both ETa and ETb is necessary to achieve maximal vasodilation. Activation of ET-B by ... 

For most purposes, capillary compliance is not taken into account. However, in some situations, such as analysis of certain capillary water transport experiments or leukocyte motion in a capillary, this view is not adequate and capillary compliance has to be accounted for. Since the capillary wall is devoid of smooth muscle cells, much of this compliance is passive, and its magnitude is small. However, the presence of contractile proteins in the cytoskeleton of capillary endothelial cells and associated pericytes opens a possibility of active capillary constriction or dilation. 

The presence of contractile protein in the endothelial cells has been known since Becker and Murphy (1969) (3,4) and among various contractile proteins, the presence of thin filaments (40-90A) with dense bodies and thick filaments (130-160A) and of intermediate filaments (70-120A) were easily recognized in the endo-... 

However, at the present moment, it seems not unreasonable to emphasize the importance of the efforts to further eludicate the nature of contractile protein within the endothelial cells of the arterial intima, and the relationship between the contraction and the endogenous cyclic AMP level, which has been already established in various smooth muscles, because the cyclic AMP phosphodiesterase inhibiting activity has been shown to be quite high in PDC and especially EG467. Also the current studies on the effects of endothelial cell relaxants on various vascular injuries must be expanded. 

Becker, C.G. and Nachman, R.L. Contractile proteins of endothelial cells, platelets and smooth muscle. 

Since endothelial and vascular smooth muscle cells can rapidly synthesize and metabolize histamine, a possible homeostatic role for histamine in cardiovascular physiology has been suggested (Gross et al., 1984). Catecholamine-stimulated histamine release from vascular tissue (Schayer, 1960 Rand et al., 1982) may function to attenuate the effect of catecholamines on heart rate, contractility, and coronary resistance (Gross et ai, 1984 Giacomini and Reis, 1986). Histamine may exert its effects on catecholamine activity by forcing an uncoupling of the P-receptor from the transductional protein, Gs (Levi et ai, 1991). 

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