No abstract

Taurine is a nonessential amino acid that has received much attention. Two organs, the heart and the brain, are known to produce their own taurine, but in very limited quantities. It is for this reason that supplementation with this amino acid is necessary. Today, taurine is present in almost all energy drinks. A very vast literature reported beneficial effects of taurine in hepatic dysfunction, gastrointestinal injury, kidney diseases, diabetes, and cardiovascular diseases. Most of its effects were attributed to its modulation of Ca2+ homeostasis as well as to its antioxidant properties. In this review, we will focus on the current status of taurine modulation of the cardiovascular system and discuss future avenues for its use as a supplement therapy in a specific cardiovascular disease, namely hypertrophy, and heart failure.

Plasma membrane endothelin type A (ET(A)) receptors are internalized and recycled to the plasma membrane, whereas endothelin type B (ET(B)) receptors undergo degradation and subsequent nuclear translocation. Recent studies show that G protein-coupled receptors (GPCRs) and ion transporters are also present and functional at the nuclear membranes of many cell types. Similarly to other GPCRs, ET(A) and ET(B) are present at both the plasma and nuclear membranes of several cardiovascular cell types, including human cardiac, vascular smooth muscle, endocardial endothelial, and vascular endothelial cells. The distribution and density of ET(A)Rs in the cytosol (including the cell membrane) and the nucleus (including the nuclear membranes) differ between these cell types. However, the localization and density of ET-1 and ET(B) receptors are similar in these cell types. The extracellular ET-1-induced increase in cytosolic ([Ca](c)) and nuclear ([Ca](n)) free Ca(2+) is associated with an increase of cytosolic and nuclear reactive oxygen species. The extracellular ET-1-induced increase of [Ca](c) and [Ca](n) as well as intracellular ET-1-induced increase of [Ca](n) are cell-type dependent. The type of ET-1 receptor mediating the extracellular ET-1-induced increase of [Ca](c) and [Ca](n) depends on the cell type. However, the cytosolic ET-1-induced increase of [Ca](n) does not depend on cell type. In conclusion, nuclear membranes' ET-1 receptors may play an important role in overall ET-1 action. These nuclear membrane ET-1 receptors could be targets for a new generation of antagonists.

Changes in reactivity to phenylephrine in aortas isolated from 2-, 6-, and 10-week ethanol-treated rats and their age-matched control and isocaloric rats were investigated. Chronic ethanol consumption enhances the contractile response of endothelium-intact and -denuded rat aortic rings to phenylephrine, a response that is time-independent. Pretreatment with indomethacin reduced E max for phenylephrine in denuded aortas from ethanol-treated rats but not control or isocaloric rats. After indomethacin treatment, no differences in E max from phenylephrine were observed among the groups.-5-heptenoic acid), an antagonist of prostaglandin H 2 /thromboxane A 2 (TXA 2 ) receptors, did not alter phenylephrine-induced contraction in control or isocaloric aortas. However, in ethanol-treated aortas, E max was reduced to control level. Moreover, phenylephrine-stimulated release of thromboxane B 2 , a stable metabolite of TXA 2 , was higher in tissues from ethanol-treated rats. Simultaneous measurement of the changes in [Ca 2ϩ ] i and contraction induced by phenylephrine showed that both parameters are higher in the rat aorta from ethanol-treated rats. CaCl 2 -induced contraction in free Ca 2ϩ solution containing phenylephrine was increased in ethanol-treated aortas. Additionally, the enhancement in CaCl 2 -induced contraction was prevented by SQ29548. The major contribution of the present study is that it demonstrates a detailed description of the mechanisms involved in the enhancement of phenylephrine-induced contraction in rat aorta from ethanol-treated rats. We provided evidence that this response was not different among the three periods of treatment employed in this study and that it is maintained by two mechanisms: an increased release of vascular smooth musclederived vasoconstrictor prostanoids (probably TXA 2 ) and an enhanced extracellular Ca 2ϩ influx.Chronic ethanol consumption is associated with cardiovascular dysfunctions independent of other known risk factors (Altura and Altura, 1982). Much of the research investigating the chronic effects of ethanol on the cardiovascular system has dealt with vascular responsiveness to vasoconstrictor agents (Strickland and Wooles, 1988;Hatton et al., 1992). Previous reports suggest that enhanced vascular reactivity to vasoconstrictor agents (Pinardi et al., 1992) or impairment of the vascular relaxation (Kahonen et al., 1999) contribute to the cardiovascular complications associated with chronic ethanol consumption.Enhanced vascular reactivity to ␣ 1 -adrenoceptor agonists was demonstrated in different arteries from ethanol-treated rats. In this line, Pinardi et al. (1992) found that chronic ethanol consumption significantly enhanced the contractile response induced by phenylephrine in aortic rings with intact endothelium. The contractile response of superior mesenteric artery to noradrenaline was shown to be greater in the rings from ethanol-treated rats (Hatton et al., 1992). Likewise, Stewart and Kennedy (1999) demonstrated an ethanol-associated increase in the m...

The action of several peptides and drugs is thought to be primarily dependent on their interactions with specific cell surface G-protein-coupled receptors and ionic transporters such as channels and exchangers. Recent development of 3-D confocal microscopy allowed several laboratories, including ours, to identify and study the localization of receptors, channels, and exchangers at the transcellular level of several cell types. Using this technique, we demonstrated in the nuclei of several types of cells the presence of Ca(2+) channels as well as Na(+)-H(+) exchanger and receptors such as endothelin-1 and angiotensin II receptors. Stimulation of these nuclear membrane G-protein-coupled receptors induced an increase of nuclear Ca(2+). Our results suggest that, similar to the plasma membrane, nuclear membranes possess channels, exchangers and receptors such as those for endothelin-1 and angiotensin II, and that the nucleus seems to be a cell within a cell. This article will emphasize these findings.