Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aortic fibronectin (FN) expression is augmented in hypertension. Increasing evidence suggests that both angiotensin II (Ang II) and mechanical factors may induce vascular remodeling in response to hypertension. We have previously shown that, in vitro, increased transmural pressure enhances FN expression in rabbit aortic media. To investigate the existence of a link between the effects of pressure and Ang II and to explore the mechanisms underlying such a relationship, we quantified the effect of Ang II and Ang II inhibitors on the pressure-dependent FN expression in a 3-day organ culture model of rabbit aorta using immunolabeling analysis and detected FN mRNAs by in situ hybridization. A dose-dependent effect of Ang II on FN expression was observed at both 80 and 150 mm Hg but not at 0 mm Hg (relaxed vessels). One mumol/L Ang II increased the media cross-sectional surface, showing FN expression from 7.9 +/- 0.7% (n = 9) to 18.9 +/- 1.1% (n = 4) at 80 mm Hg (P < .01) and from 17.4 +/- 1.8% (n = 9) to 56.6% +/- 3.6 (n = 4) at 150 mm Hg (P < .001). In situ hybridization revealed that Ang II and pressure upregulated FN mRNA expression. Losartan, an AT1 antagonist, not only blocked the Ang II effect but also inhibited the transmural pressure effect. Angiotensin-converting enzyme inhibition abolished the pressure-dependent FN expression and significantly diminished the effect of pressure in the presence of Ang II. The effect of renin-angiotensin system inhibitors was specific for FN, since neither bFGF nor laminin expression was affected by these agents. Taken together, the results demonstrate that (1) the effect of transmural pressure is mediated by the stimulation of a local renin-angiotensin system, resulting in a net Ang II production in the culture medium, (2) transmural pressure and Ang II act synergistically to enhance vascular FN expression, (3) AT1 receptors mediate both the effects of pressure and of exogenous Ang II, and (4) the effect of Ang II on FN expression is regulated at a pretranslational level.
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PMID:Pressure and angiotensin II synergistically induce aortic fibronectin expression in organ culture model of rabbit aorta. Evidence for a pressure-induced tissue renin-angiotensin system. 892 71

There is compelling evidence supporting the renin-angiotensin-aldosterone system contribution in experimental and human renal disease. Interruption of this system by converting enzyme inhibition or angiotensin II receptor antagonism reduces injury. Angiotensin II contributes to the progression of renal disease through its direct vascular effects and proliferative properties. The mediators of angiotensin II induced renal injury are many and include TGF-beta, PDGF, bFGF, and endothelin. Though the mechanisms involved in its contribution to progressive renal disease are not well delineated, aldosterone seems to be an overlooked contributor to the progression of kidney disease and its effects may also depend on both its hemodynamic and more direct cellular actions.
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PMID:Aldosterone is a major factor in the progression of renal disease. 940 37

The stimulation of the zona glomerulosa phenotype by a low sodium diet is characterised by increased expression of aldosterone synthase accompanied by increases in (pro)renin, bFGF, c-fos and c-jun gene transcription. In contrast ACTH diminishes the specific glomerulosa phenotype. The EGF related transmembrane protein preadipocyte factor 1 (Pref-1) is specifically found in the zona glomerulosa and medulla of the adult rat adrenal as well as being expressed in fetal tissue. In addition the orphan nuclear receptor SF-1/Ad4bp considered to be an important factor in fetal adrenocortical development and differentiation may also have a role in zonal differentiation in the adult. To investigate their roles, adrenals were taken from adult Wistar rats maintained on a low sodium diet or ACTH treated (enhancing or diminishing zona glomerulosa function respectively) and compared with untreated controls. Localisation of Pref-1 was carried out by immunocytochemistry using the polyclonal antibody ZOG (anti Pref-1) and of SF-1 using a rabbit antiserum to SF-1. The experimental treatment resulted in a decrease and increase in Pref-1 expression in ACTH treated and low sodium diet treated rats respectively, in accordance with changes in abundance of glomerulosa cells. SF-1 expression was expected throughout the adrenal cortex, without zonal differentiation, though somewhat decreased by ACTH treatment. Of these two factors, only Pref-1 can be considered to have a role in zonal differentiation.
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PMID:Pref-1, SF-1 and adrenocortical zonation. 988 10

Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the actions of ACTH in normal animals. In contrast, IGF-I enhances the glomerulosa secreting phenotype and diminishes that of the fasciculata/reticularis, possibly replicating the actions of angiotensin II or a low sodium diet.
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PMID:Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study. 1039 17

Preliminary studies by our group and others indicate that angiotensin II may have an important role in the cellular regulation of smooth muscle growth and collagen production in the bladder. The exact mechanisms in which angiotensin II elicits its cellular effects are not known. Given the available information thus far, we hypothesize the following (see Figure 2): 1) Outlet obstruction of the bladder causes increased cell stretch/strain which in turn induces the local production of angiotensin II. Angiotensin II may also influence cell stretch/strain via its direct effects on bladder tone. 2) Angiotensin II then acts as a trophic factor in the bladder wall to cause smooth muscle cell hypertrophy/hyperplasia and increased collagen production via an autocrine and/or paracrine pathway. 3) The cellular effect(s) of angiotensin II may be mediated by secondary growth factors such as bFGF and TGFb Much more extensive research is certainly needed to reveal whether some part, or all of this hypothesis is correct. If angiotensin II is indeed active in regulating muscle and collagen changes in the pathologic bladder, then the clinical implications are extremely exciting since numerous pharmacologic agents are now available which can either inhibit angiotensin II production and/or block receptor mediated events. These agents may prove to be extremely useful in the clinical management of the neurogenic bladder in which obstructive changes may be prevented and potentially reversed. Despite this, caution must be exercised with regard to the potential use of any medications which alter the systemic renin-angiotensin system in the pediatric population since some research has suggested that an intact system may be necessary for the normal development of some organs, including the kidney.
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PMID:Role of angiotensin II in bladder smooth muscle growth and function. 1059 23