ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Angiotensin II has emerged as an important growth factor for vascular, cardiac, and renal cells. Depending on the specific cell type and presence of other growth factors, angiotensin II induces proliferation (replication of DNA with subsequent successful division of cells), hypertrophy (increase in cell size, cell protein, and mRNA content without DNA replication), apoptosis (programmed cell death), or differentiation. Such angiotensin II-mediated modulation of growth process may underlie various pathophysiological processes such as atherosclerosis, vascular and cardiac remodeling, and progression of chronic renal disease. Clearly, angiotensin II-induced proliferation requires complete cell progression through the various steps of the cell cycle. In contrast, cells undergoing angiotensin II-mediated hypertrophy are arrested in the G1-phase. Upregulation of cell cycle-dependent kinase inhibitors (eg, p27Kip1) plays an important role in this process. Although accumulating evidence suggests that apoptosis is cell cycle-dependent, only few data are currently available concerning the interaction of angiotensin II with the cell cycle machinery in apoptosis. We review the various angiotensin II-mediated growth processes and their relationship to events governing cell cycle regulation.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only caused by hypertension. Another characteristic of renal disease is unbalanced nitric oxide (NO) and angiotensin (Ang) activity. Increased SNA in renal disease may be sustained because a state of NO–Ang II unbalance is also present in the hypothalamus. Very few studies have directly compared the efficacy of adrenergic blockade with other renoprotective measures. Third-generation &bgr;-blockers seem to have more protective effects than traditional &bgr;-blockers, possibly via stimulation of NO release. Although it has been extensively documented that muscle SNA is increased in chronic renal failure, data on renal SNA and cardiac SNA are not available for these patients before end-stage renal disease. It is also unknown whether additional treatment with third-generation &bgr;-blockers can delay the progression of renal injury and prevent cardiac injury in chronic renal failure more efficiently than conventional treatment with angiotensin-converting enzyme inhibitors only.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Based on racial differences in urinary potassium excretion and responses to diuretics, we present a model suggesting that a major cause of sodium sensitivity in blacks is an augmented activity of the Na-K-2Cl cotransport in the thick ascending limb of Henle’s loop. This would result in an increased ability to conserve not only sodium but also water, and an upward and rightward shift in the operating point of tubuloglomerular feedback, which may cause an increase in the glomerular capillary hydraulic pressure and predilection to glomerular injury with and without hypertension. In this sense, the biological implication of sodium sensitivity in blacks and in humans in general has ramifications above and beyond salt-evoked increase in blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Excessive deformation of vascular smooth muscle cells (SMCs) caused by a prolonged increase in blood pressure (eg, in hypertension) results in an adaptive remodeling of the vessel wall that is characterized by SMC hypertrophy or hyperplasia and contributes to fixation of the increase in blood pressure. The onset of this process is characterized by a unique change in gene expression in the SMC. However, thus far, no transcription factor has been identified that specifically mediates mechanosensitive gene expression in these cells. Therefore, the role of a putative mechanotransducer, the cytoskeletal protein zyxin, was investigated in rat aortic cultured SMCs. Immunofluorescence and Western blot analysis revealed that on exposure to cyclic stretch, but not to osmotic stress or treatment with proinflammatory cytokines, zyxin dissociates from focal adhesions and accumulates in the nucleus. Unlike zyxin, vinculin, another focal adhesion-associated protein, did not translocate. Moreover, antisense oligonucleotide downregulation of zyxin protein abundance suggested that zyxin accumulation in the nucleus is a prerequisite for mechanosensitive gene expression in these cells. Thus, stretch-induced endothelin B receptor expression, for example, was attenuated, whereas that of tenascin-C was augmented after zyxin suppression. The data are consistent with a role for zyxin in transducing mechanical stimuli from the cell membrane to the nucleus in vascular SMCs and in controlling the expression of mechanosensitive genes that have been implicated in hypertension-induced arterial remodeling.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID