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)

As the interlobular arteries of the ageing kidney progressively accumulate intimal fibroplasia, these fibroplastic changes appear to introduce strictures upon the interlobular arteries. These strictures are expected to generate nephron heterogeneity, which is a uniquely disturbed setting peculiarly suited to sustaining both high and low renin forms of hypertension. Fibroplastic renovasculopathy accumulates with age at varying rates in different human populations, and these rates closely parallel the rise of blood pressure with age, as documented by community surveys. Here, I introduce the expression type 1 for hypertension in subjects with mild or minimal renovasculopathy, and type 2 for those with severe vasculopathy. Data reviewed here imply that variations in prevailing blood pressure levels between populations can be attributed entirely, or almost entirely, to type 2 hypertension. No practical test is available to detect nephron heterogeneity clinically. Tests for this purpose have not been and are not now in development. The reason for this deficiency is probably the general lack of suspicion regarding the existence of this pathological entity. Once the entity becomes the target of attention, a variety of tests for measuring its severity in clinical patients should follow readily.
Nephrol Dial Transplant 1999 Jul
PMID:The heterogeneity of vascular findings in the kidneys of patients with benign essential hypertension. 1043 70

ACE-I and specific ETA receptor blockade comparably prevented the development of structural cardiovascular alterations such as LVH, myocardial interstitial expansion and wall thickening of intramyocardial and extracardiac arteries in experimental renal failure. However, the decrease in myocardial capillary supply and the concomitant increase in intercapillary distance could only be prevented by ETA receptor antagonism. These capillary changes which have been shown to occur in experimental renal failure as well as in uraemic patients play an important role in the pathogenesis of reduced cardiac ischaemia tolerance in renal failure. The data argue for a potential role of the local renin-angiotensin system as well as of the ET system in the pathogenesis of cardiovascular changes in renal failure and for ET receptor blockade as a new therapeutic option in the treatment of these alterations. In particular, myocardial capillary supply, which is particularly important for ischaemia tolerance in renal failure, seems to be modulated and regulated predominantly by ET-1. In contrast to what was found with respect to structural and functional changes of the kidney in various experimental models of renal damage, a combination therapy--at least in the doses used--does not seem to provide additional benefit in the prevention of cardiovascular changes compared with the respective monotherapies.
Nephrol Dial Transplant 1999
PMID:Treatment of cardiovascular changes in renal failure--ACE inhibition, endothelin receptor blockade or a combination of both strategies? 1046 13

The 825T allele of the gene GNB3 which encodes the beta 3 subunit of heterotrimeric G proteins is associated with enhanced signal transduction via G proteins through the generation of a splice variant termed Gbeta3s. It was detected following a classical candidate gene approach using cell lines from patients with enhanced signal transduction and essential hypertension. The high frequency of the 825T allele in 'old' ethnicities, e.g. bushmen and Australian aborigines as well as in black populations, together with its strong association with obesity suggests that the 825T allele is a true 'thrifty genotype'. Development of obesity associated with the 825T allele is strongly influenced by lifestyle, e.g. physical activity, and other exogenous influences like pregnancy. In hypertension the 825T allele is associated with low renin activity and appears to strongly predict the development of left ventricular hypertrophy. In type 2 diabetes the 825T allele was reported to be predispose for end-stage renal disease, whereas this effect has not yet been confirmed for patients with type 1 diabetes.
Nephrol Dial Transplant 2000 Sep
PMID:G protein beta 3 subunit 825T allele, hypertension, obesity, and diabetic nephropathy. 1139 Jul 42

Angiotensin-(1-7) [Ang-(1-7)], which can be formed directly from angiotensin I (Ang I) bypassing the requisite production of Ang II, is a bioactive component of the renin-angiotensin system that may oppose the actions of Ang II. In contrast to the generation of Ang II, angiotensin-converting enzyme (ACE) hydrolyses Ang-(1-7) to inactive fragments. ACE inhibitors substantially augment circulating levels of Ang-(1-7) and increase the peptide's half-life. Thus, this enzymatic pathway constitutes a key regulatory point in the vasculature to balance the actions of Ang II, Ang-(1-7) and bradykinin. In contrast, the renal pathways for the metabolism of Ang-(1-7) appear quite distinct. Characterization of this pathway may shed new light on the potential actions of the peptide in the kidney, as well as the mechanisms of novel vasoactive peptidase therapies. We summarize recent experimental and clinical studies that begin to reveal novel pathways in the formation and degradation of Ang-(1-7) in the kidney.
Nephrol Dial Transplant 2001
PMID:Pathways of angiotensin-(1-7) metabolism in the kidney. 1136 16

Endothelial nitric oxide synthase (eNOS) serves a number of functions in the vasculature. In response to stimuli such as shear stress or acetylcholine, eNOS catalyses the production of nitric oxide (NO) from L-arginine. The NO diffuses across the endothelium into neighbouring smooth muscle and induces vasodilation. NO also acts locally to prevent platelet and leucocyte aggregation and inhibits vascular smooth muscle cell proliferation. It has been shown that mice lacking eNOS have decreased blood pressure, decreased heart rate and increased plasma renin activity. It has also been reported that NO production was reduced in patients with essential hypertension compared with normotensive individuals. In several animal models of renal disease (subtotal renal ablation, ureteral obstruction and diabetes), the administration of L-arginine, and probably the increase in NO synthesis, reduced the degree of glomerulosclerosis, ameliorated the changes in the tubulointerstitial compartment of the kidney and also decreased the infiltration of the kidney by invading macrophages. In summary, the L-arginine-NO pathway plays an important role in hypertension, renal disease, inflammation and atherosclerosis. This pathway also interacts with the renin-angiotensin system, the eicosanoid pathway, endothelin, cytokines and regulators of inflammation such as NF-kappaB.
Nephrol Dial Transplant 2001
PMID:The role of nitric oxide in hypertension and renal disease progression. 1136 23

Hypertension leads to renal disease through a series of mechanisms that seem to be exaggerated in African-Americans, who have a higher prevalence of both hypertension and end-stage renal disease than whites. Renal disease itself leads to hypertension, which in turn can contribute to progression of renal disease. Although there are numerous mechanisms involved in the process of renal disease progression, the renin-angiotensin system plays a major role as determined by the beneficial response to angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (AT II blockers) of reduced rate of progression in a variety of clinical and experimental renal diseases. Macromolecular trafficking across the glomerulus leading to proteinuria plays a significant role in progression of chronic renal disease. Reversal of this abnormality and reduced stress on capillary walls may be the major mechanisms of beneficial action of ACEIs and AT II blockers in halting renal disease progression.
Nephrol Dial Transplant 2001
PMID:Role of hypertension in the progression of chronic renal disease. 1136 24

In the past, it had been presumed that hypertension in chronic renal disease can be explained by the dual effects of sodium retention and inappropriate activity of the renin-angiotensin system. Recent experimental and clinical data provide strong evidence that the increase in blood pressure is to a large part due to sympathetic overactivity which is triggered by afferent signals emanating from the kidney and resetting sympathetic tone by stimulation of hypothalamic centres. The sequelae of sympathetic overactivity extend beyond their effects on blood pressure and include accelerated progression of renal failure and presumably increased cardiac arrhythmia.
Nephrol Dial Transplant 2001
PMID:Sympathetic overactivity and arterial hypertension in renal failure. 1136 25

Chronic allograft nephropathy is the principal cause of late graft loss after the first year of renal transplantation. Transforming growth factor-beta1 (TGF-beta1) is a key fibrogenetic cytokine involved in the fibrosis of a number of chronic diseases of the kidney and other organs, and recently evidence has shown that TGF-beta1 is involved in the pathogenesis of chronic renal allograft dysfunction. Production of TGF-beta1 in these circumstances may be modulated by the intrarenal renin-angiotensin system (angiotensin II induces TGF-beta1 production and secretion by the mesangial cells) and by a direct effect of cyclosporin A, which stimulates the synthesis and expression of TGF-beta1. In a prospective study of 14 renal transplant patients exhibiting chronic graft nephropathy, we demonstrated that treatment with losartan significantly decreased plasma levels of TGF-beta1 by >50%. There was a significant correlation (P=0.04) between the increase in circulating angiotensin II after 2 weeks and the decrease in plasma TGF-beta(1) at the end of the study period, suggesting that the degree of angiotensin II receptor blockade plays a decisive role in the synthesis of TGF-beta1. A significant decrease in circulating endothelin-1 (ET-1) levels also occurred during treatment with losartan, together with a decrease in proteinuria. In a randomized 2x2 crossover study, the effects of losartan and amlodipine on renal haemodynamics and on profibrogenetic cytokines were analysed. Whereas amlodipine increased the glomerular filtration rate (GFR) through an increase in the FF and P(G), losartan slightly decreased the GFR, but with a significant decrease in FF and P(G). With respect to the profibrogenetic cytokines, losartan decreased the plasma levels of TGF-beta1 and ET-1, while amlodipine did not significantly change TGF-beta1 and slightly increased ET-1.
Nephrol Dial Transplant 2001
PMID:Role of transforming growth factor-beta1 in the progression of chronic allograft nephropathy. 1136 37

The present study was carried out to investigate changes in the expression of aquaporins (AQPs) in the peritoneum. The effects of the renin-angiotensin system on the expression of AQPs with and without angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type 1a receptor blocker (ARB) were then examined. We divided 20 male Wistar Kyoto (WKY) rats into four groups, dialyzed with these solutions: saline; 10% glucose (TZ); 10% glucose plus benazepril (ACEI: 4 mg/kg daily); and 10% glucose plus valsartan (ARB: 10 mg/kg daily). The ACEI and ARB were administered into the peritoneum for 7 days. Expression of AQP-1-AQP-4 mRNA was studied by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Ultrafiltration volume (UFV) and peritoneal function were measured by peritoneal equilibration test (PET). In the TZ group, expression of AQP-1 and AQP-4 was enhanced in parallel with an increment in UFV. Expression of AQP-1 and AQP-4 was also observed in the mesothelium by immunofluorescence microscopy. On the other hand, in ACEI- and ARB-treated rats, expression of AQP-1 and AQP-4 was significantly suppressed, accompanied by loss of UFV. Our results suggest that the renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum. Administration of ACEI or ARB in patients undergoing continuous ambulatory peritoneal dialysis should be carried out with caution.
Adv Perit Dial 2001
PMID:Renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum. 1151 Feb 75

Accumulating evidence suggests that angiotensin II (ANG II) plays an important role in the complex affair of renal organogenesis. The renin-angiotensin system (RAS) is up-regulated during renal development and in the perinatal period. On the other hand, inhibition of the RAS, for example by angiotensin-converting enzyme (ACE) inhibitors, may produce specific renal abnormalities including abnormal renal vessels, failure to develop a renal pelvis and tubular atrophy associated with expansion of the interstitium. AT2 receptors are expressed abundantly during fetal development and are down-regulated markedly after birth, whereas the abundance of AT1 receptors increases as maturation proceeds. Mice with targeted deletions of genes for angiotensinogen or ACE revealed severe renal abnormalities. In contrast, AT1A, AT1B and AT2 receptor knockout animals exhibited milder abnormalities of the kidney. These findings suggest that AT1 and AT2 receptors are both involved in the development of the nephron, and that ANG II provides signals through both receptors. ANG II exerts in vitro growth-stimulatory effects on tubular cells. Moreover, ANG II induces synthesis of collagen type IV in tubular cells, a necessary prerequisite for successful basement membrane formation. These effects are mediated through AT1 receptors. Thus, it is feasible that blockade of the RAS during kidney organogenesis leads to a decrease in the growth factor ANG II that may be pivotal for tubular growth and differentiation. On the other hand, ANG II's growth-stimulatory effects through AT1 receptors may be counterbalanced by AT2 receptor-mediated apoptosis and growth inhibition. Therefore, alterations in AT2 receptor signalling may alter the delicate balance between growth stimulation and inhibition, leading to alterations in tubular formation.
Nephrol Dial Transplant 2002
PMID:Angiotensin II and tubular development. 1238 87


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