Tolerance to ethanol-induced contractions of vascular smooth muscle: Role of endothelium

Ethanol, at high concentrations, produced a dose-dependent contraction of male rat aortic rings, $\text{in vitro}$. Mechanical removal of endothelial cells from aortic rings of control rats resulted in a small, but significant, shift of the ethanol dose-response curve to the right without a change in the maximal contraction. Removing the endothelial cells of aortic rings obtained from rats intoxicated with ethanol for two days significantly shifted the ethanol dose-response curve to the left and significantly increased the maximal contraction induced by ethanol. A comparison of the ethanol dose-response curves in aortic rings with endothelium obtained from control rats with those obtained from intoxicated rats indicated a significant shift to the right with no change in maximal response. No significant changes were observed when the responses of aortic rings without endothelium obtained from control and intoxicated rats were compared. These observations confirm that tolerance to ethanol can be demonstrated in vascular smooth muscle. In addition, they demonstrate that the endothelium is required for the development of tolerance to ethanol in the aorta.     

Role of myocardium and endothelium in coronary vascular smooth muscle responses to hypoxia

Hypoxia triggers a mechanism that induces vasodilation in the whole heart but not necessarily in isolated coronary arteries. We therefore studied the role of cardiomyocytes (CM), smooth muscle cells (SMC), and endothelial cells (EC) in coronary responses to hypoxia (PO(2) of 5-10 mmHg). In an attempt to determine the factor(s) released in response to hypoxia, we inhibited the contribution of adenosine, ATP-sensitive K(+) channels, prostaglandins, and nitric oxide. Isolated rat septal artery segments without (-T) and with a layer of cardiac tissue (+T) were mounted in a double wire myograph, and constriction was induced. Hypoxia induced a decrease in isometric force of 21% and 61% in -T and +T segments, respectively (P < 0.05). EC removal increased the relaxation to hypoxia in -T segments to 33% but had the same effect in +T segments (61%). Only one of the inhibitors, the adenosine antagonist in +T segments, partially affected the relaxation due to hypoxia. The role of adenosine is thus limited and other mechanisms have to contribute. We conclude that hypoxia induces a relaxation of SMC that is augmented by the presence of CM and blunted by the endothelium. A single mediator does not induce those effects.     

Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus.

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.     

The sodium pump in opossum vascular smooth muscle

Ouabain-sensitive Rb+ uptake and [3H]ouabain binding were used to measure rates of Na+ pumping and the number of pump sites, respectively, in thoracic aortae from opossums. From the number of Rb+ ions pumped per site per minute, estimates of pump turnover have been made. Values obtained are comparable to those of other species (see Table 1).     

Thick filaments in vascular smooth muscle

Two sets of myofilaments were demonstrated after incubation of strips of rabbit portal-anterior mesenteric vein under moderate stretch in a physiological salt solution. Thick filaments had a mean diameter of 18 nm and reached a maximum length of 1.4 µm with a mean length of 0.61 µm. In transverse sections, 2.5–5 nm particles were resolved as subunits of the thick filaments. Thin filaments had an average diameter of 8.4 nm and generally conformed to the structure believed to represent actin filaments in smooth and striated muscles. In the areas of maximum concentration there were 160–328 thick filaments/µm² and the lowest ratio of thin to thick filaments was 12:1. Thick filaments were present in approximately equal numbers in vascular smooth muscle relaxed by theophylline, in Ca⁺⁺-free solution, or contracted by norepinephrine. The same preparatory procedures used with vascular smooth muscle also enabled us to visualize thick filaments in guinea pig and rabbit taenia coli and vas deferens.     

TRAIL expression in vascular smooth muscle

TRAIL is a cell-associated tumor necrosis factor-related apoptosis-inducing ligand originally identified in immune cells. The ligand has the capacity to induce apoptosis after binding to cell surface receptors. To examine TRAIL expression in murine vascular tissue, we employed in situ hybridization and immunohistochemistry. In these studies, we found that TRAIL mRNA and protein were specifically localized throughout the medial smooth muscle cell layer of the pulmonary artery. Notably, a similar pattern of expression was observed in the mouse aorta. Consistent with these findings, we found that cultures of primary human aorta and pulmonary artery smooth muscle cells express abundant TRAIL mRNA and protein. We also found that these cells and endothelial cells undergo cell lysis in response to exogenous addition of TRAIL. Last, we confirmed that TRAIL specifically activated a death program by confirming poly(ADP ribose) polymerase cleavage. Overall, we believe that these findings are relevant to understanding the factors that regulate cell turnover in the vessel wall.     

The superficial buffer barrier in vascular smooth muscle.

Force development and fura-2 fluorescence were simultaneously measured in the rabbit inferior vena cava. Discharging SR Ca2+ with either caffeine or norepinephrine prior to stimulation of Ca2+ influx induced a delay of 30-70 s between the intracellular Ca2+ signal and development of force. This delay was abolished by the application of caffeine. These data support the superficial buffer barrier hypothesis, which holds that Ca2+ entry from the extracellular space proceeds via a restricted cytoplasmic region between the inner plasmalemmal surface and the peripheral sarcoplasmic reticulum (SR). Ca2+ accumulation by this SR fraction appears to be able to delay Ca2+ entry into the deeper myoplasm where it activates the myofilaments. Caffeine and thapsigargin elevated the steady-state [Ca2+]i, suggesting a contribution by the SR Ca2+ pump to Ca2+ extrusion from the cells. Norepinephrine enhanced myofilament Ca2+ sensitivity, while caffeine decreased it.     

血管平滑肌细胞在动脉粥样硬化中的作用

动脉粥样硬化的发生发展是一个复杂的过程,涉及到多种细胞及细胞因子的相互作用.平滑肌细胞作为血管壁的重要成分,调节着血管的收缩舒张功能,同时也分泌多种细胞因子及细胞间质;它的生物学行为对动脉粥样硬化的发生、发展及最终的结局产生着重要的影响.本文就平滑肌细胞的生物学行为的变化及其在动脉粥样硬化的不同发展阶段的作用进行综述.     

The many ways of Wnt in cancer

More than 20 years ago, the oncogenicity of a Wnt ligand was revealed in a series of experiments originating with random proviral integration in mice. The significance of Wnt signaling in human cancer has since been buttressed by the identification of mutations in genes coding for the Wnt pathway components Axin, APC, and beta-catenin. This review summarizes the reported genetic defects in the Wnt pathway, with an emphasis on their functional contribution to human tumor progression.     

Heparin interactions with cultured human vascular endothelial and smooth muscle cells: incidence on vascular smooth muscle cell proliferation

The binding, internalization, and metabolism of [3H]-heparin by human umbilical vein endothelial cells (HUVEC) and human umbilical arterial smooth muscle cells (HUASMC) have been characterized using size-exclusion HPLC. Incubation of HUVEC with [3H]-heparin demonstrated selective binding of high-molecular-weight (MW) components (MW = 21 kd), which was followed by rapid, temperature-dependent internalization. Over the next 3 hours, this internalized [3H]-heparin was degraded to low-MW fragments (MW = 0.9 kd). Primary cultures of HUASMC selectively bound extremely high-MW components (MW = 40 kd) and also smaller components whose MW (0.9 kd) corresponded to that of the heparin metabolite(s) formed by HUVEC. Subcultured HUASMC bound only the 40-kd components. Internalization of heparin by smooth muscle cells (SMC) was significantly slower than that determined for HUVEC, and even after 4 hours there was no evidence of the heparin being metabolized. However, when incubating primary rabbit aortic SMC with purified low-MW heparin fragment(s) produced in culture by HUVEC, a significantly lower proliferative response of these cells (IC50 = 18.4 micrograms/ml) was obtained. Virtually no effect was observed with subcultured SMC in the range of the tested concentrations (0-20 micrograms/ml). These fragments were 10- to 15-fold more effective in inhibiting primary SMC growth than was standard heparin. Furthermore, heparin fractions in the same range of molecular weights, purified either after nitrous acid or heparinase depolymerization of standard heparin, showed no activity on primary SMC growth, thus indicating a high degree of selectivity of the heparin metabolite(s) produced by HUVEC in culture.     

The many ways to cleave hyaluronan

Hyaluronan is being used increasingly as a component of artificial matrices and in bioengineering for tissue scaffolding. The length of hyaluronan polymer chains is now recognized as informational, involving a wide variety of size-specific functions. Inadvertent scission of hyaluronan can occur during the process of preparation. On the other hand, certain size-specific hyaluronan fragments may be desirable, endowing the finished bioengineered product with specific properties. In this review, the vast arrays of reactions that cause scission of hyaluronan polymers is presented, including those on an enzymatic, free radical, and chemical basis.     

Oxygen-dependent signaling in pulmonary vascular smooth muscle

The pulmonary circulation constricts in response to acute hypoxia, which is reversible on reexposure to oxygen. On exposure to chronic hypoxia, in addition to vasoconstriction, the pulmonary vasculature undergoes remodeling, resulting in a sustained increase in pulmonary vascular resistance that is not immediately reversible. Hypoxic pulmonary vasoconstriction is physiological in the fetus, and there are many mechanisms by which the pulmonary vasculature relaxes at birth, principal among which is the acute increase in oxygen. Oxygen-induced signaling mechanisms, which result in pulmonary vascular relaxation at birth, and the mechanisms by which chronic hypoxia results in pulmonary vascular remodeling in the fetus and adult, are being investigated. Here, the roles of cGMP-dependent protein kinase in oxygen-mediated signaling in fetal pulmonary vascular smooth muscle and the effects of chronic hypoxia on ion channel activity and smooth muscle function such as contraction, growth, and gene expression were discussed.     

血管平滑肌细胞的钙动力学

血管平滑肌细胞外的Ca~(2+)通过多种通道进入细胞内。Ca~(2+)通道的本质是镶嵌在膜脂质双分子层中的糖蛋白,神经介质和药物可影响Ca~(2+)通道的功能。靠近胞膜的肌质网和胞膜内侧面的高亲和性Ca~(2+)结合位点是血管平滑肌细胞内储存和释放Ca~(2+)的主要部位。胞浆[Ca~(2+)]增高后在钙调蛋白的介导下引起血管收缩。高血压等血管性疾病的发生与其平滑肌细胞的钙动力学异常有关。