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

In male heterozygous transgenic hypertensive rats, TGR(mREN2)27 (TGR), exhibiting an inverse blood pressure profile and in normotensive Sprague-Dawley (SPRD) controls, the density and affinity of angiotensin II receptors were determined at six circadian times in glomeruli of animals 11 weeks old kept under light-dark 12h:12 (LD 12:12) conditions. Angiotensin II receptors were also studied in rats 18-20 weeks old of both strains at 2h after light onset. As a measure of renal excretory functions, diuresis, creatinine, and protein excretion were monitored using metabolic cages. The expression of angiotensin II receptor mRNA was determined in renal arteries 2h-4h after light onset. The following results were obtained: (1) Renal excretory functions showed significant daily variation, with higher excretion rates in the dark span in both TGR and SPRD rats. (2) No circadian phase dependency was found in the glomerular angiotensin II receptors in both rat strains. However, receptor density was significantly lower in TGR than in SPRD rats. In both strains, receptor number increased with aging. (3) In renal arteries, the angiotensin II receptor mRNA of the main receptor subtype AT1A was neither strain nor age dependent, AT1B- and AT2-receptor mRNAs were significantly lower in TGR than SPRD rats. In conclusion, the results demonstrate that the overactive renin-angiotensin system in TGR rats led to a down-regulation of glomerular angiotensin II receptors that was not accompanied by a down-regulation of the mRNA of the dominant AT1A- receptor subtype. Circadian short-term variations in blood pressure in both TGR and SPRD rats are not reflected by daily variation in angiotensin II receptor density of renal glomeruli or by variation in receptor expression in renal vascular tissue.
 ...
PMID:Influence of circadian time and age on glomerular angiotensin II receptors in normotensive Sprague-Dawley and transgenic hypertensive TGR(mREN2)27 rats. 1147 15

Plasminogen activator inhibitor type-1 (PAI-1) is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular disease, as well as of other arterial and venous thromboembolic diseases. Recently, an important role of elevated pretreatment levels of PAI-1 for failure of thrombolytic therapy of acute myocardial infarction has been discussed. PAI-1 plasma levels depend on the one hand on gene regulation but are related on the other hand to known risk factors of atherosclerosis like insulin resistance, diabetes or hypertriglyceridemia, respectively. Furthermore, an activated renin-angiotensin-aldosterone system (RAAS) significantly contributes to the upregulation of PAI-1 concentration via a receptor-mediated mechanism. In accordance to the known mechanisms of regulation of PAI-1 plasma levels, the use of specific agents like antidiabetic drugs, fibrates, statins, ACE inhibitors and angiotensin II type-1 receptor-blockers may contribute to the downregulation of circulating PAI-1 and, therefore, increase the fibrinolytic capacity and consecutively counteract the thrombotic tendency. To further improve the efficacy of thrombolytic therapy, a PAI-1 resistant variant of t-PA, TNK-t-PA, has been developed and is now available for acute myocardial infarction.
 ...
PMID:Plasminogen activator inhibitor type-1 in cardiovascular disease. Status report 2001. 1156 64

The purpose of this study was to examine the relationship between carotid intima-media thickness (CIMT) interindividual variability and 16 polymorphisms of 11 genes associated with cardiovascular risk factors (genes among lipid and homocysteine metabolisms, blood viscosity, platelet aggregation, leukocyte adhesion and renin-angiotensin system). CIMT was measured by high resolution B mode ultrasonography in an healthy population of 77 men and 84 women, aged 35-54 years and selected from a French cohort: the Stanislas cohort. The polymorphisms studied were genotyped by a multilocus approach. Statistical analysis were done by ANOVA after adjustment of CIMT for age, BMI and smoking and by multiple regression analyses. No association was found with APOB Thr71 Ile, APOC3 -482C/T, -455T/C, GpIIIa P1A, AT1R 1166A/C, AGT Met235Thr, CBS Ile278Thr, SELE 98G/T and SELE Ser128Arg, polymorphism neither in men nor in women. Although, in women we found always no association for the APOC3 3206T/G, 3175C/G, 1100C/T, the CETP Ile405Val, the MTHFR 677C/T and the fibrinogen -455G/A polymorphism's, in men these polymorphism's were associated with CIMT variability (0.01 < or = p < or = 0.05). The most interesting finding was that altogether these genes in men were able to explain a considerable part, 20.6%, of CIMT variability. Therefore, our study gives a new opportunity to understand CIMT variability.
 ...
PMID:[APOC3, CETP, beta-fibrinogen and MTHFR are genetic determinants of carotid intim-media thickness (Stanislas cohort)]. 1157 17

In wild-type mice, 2-wk administration of losartan, an angiotensin (Ang) II type 1 (AT1) receptor antagonist, along with dietary sodium restriction, resulted in an elevation of plasma aldosterone greater than that seen with sodium restriction alone (2.75 +/- 0.35 vs. 1.38 +/- 0.16 ng/ml, P < 0.01). Plasma potassium increased in sodium-restricted, losartan-treated mice (6.0 +/- 0.2 mEq/liter), while potassium remained unchanged in mice with sodium restriction alone. To study the effect of Ang II on glomerulosa cells that may operate independently of plasma potassium in situ, we used chimeric mice made of cells with or without the intact AT1A gene (Agtr1a). When animals were fed a normal diet or chronically infused with Ang II, the aldosterone synthase mRNA was detectable only in Agtr1a+/+ but not Agtr1a-/- zona glomerulosa cells. After 2 wk of sodium restriction, plasma aldosterone increased (1.51 +/- 0.27 ng/ml) and potassium remained on average at 4.5 +/- 0.2 mEq/liter, with aldosterone synthase mRNA expressed intensively in Agtr1a+/+, but not detectable in Agtr1a-/- cells. Simultaneous sodium restriction and losartan treatment caused increases in plasma potassium (5.5 +/- 0.1 mEq/liter) and aldosterone (1.84 +/- 0.38 ng/ml), with both Agtr1a-/- and Agtr1a+/+ cells intensively expressing aldosterone synthase mRNA. Thus, aldosterone production is regulated by Ang II in the adrenal gland during chronic alterations in extracellular fluid volume when plasma potassium is maintained within the normal range. In the light of a previous observation that dietary potassium restriction superimposed on sodium restriction abolished secondary hyperaldosteronism in angiotensinogen null-mutant mice, the present findings demonstrate that when the renin-Ang system is compromised, plasma potassium acts as an effective alternative mechanism for the volume homeostasis through its capacity to induce hyperaldosteronism.
 ...
PMID:In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion. 1173 22

Delayed graft function (DGF), defined as persistent renal failure that requires dialysis within the first week after kidney transplantation, occurs commonly after cadaveric renal transplantation (CRT). This has important implications for long-term outcome because the 1-year allograft survival rate is significantly reduced when DGF occurs. The mechanisms contributing to the development of DGF are not well established. However, several lines of evidence indicate that excess renin system activity, in both the cadaver kidney donor and recipient, contributes importantly to the pathogenesis of DGF. If this hypothesis can be verified in clinical studies, then pharmacologic agents that interrupt the renin-angiotensin system (eg, type 1 angiotensin II receptor blockade, angiotensin converting enzyme inhibition, and beta-adrenergic blockade) in the donor and recipient might significantly improve the outcome of cadaveric renal transplants.
 ...
PMID:Renin system activation and delayed function of the renal transplant. 1177 37

CS-866 is an angiotensin II type-1 receptor antagonist, the effects of which on systolic blood pressure (BP) and glucose/insulin metabolism are investigated under hyperlipidaemic conditions produced by cholesterol feeding. Thirty-two female Japanese White rabbits (two months old) were assigned randomly into a CS-866-treated group (n = 17) fed a food admixture that contained 0.03% CS-866 and 0.2% cholesterol, or into a control group (n = 15) fed a food admixture containing 0.2% cholesterol only. Systolic BP was measured by an ear-cuff method. Glucose and insulin metabolism was characterised quantitatively from the results of an intravenous glucose tolerance test by a minimal model technique reported previously. After six months treatment, systolic BP in the CS-866-treated group was lower than in the control group (105 +/- 14 mmHg versus 115 +/- 18 mmHg; P <0.05), as assessed by analysis of variance and the Wilcoxon rank-sum test. No significant differences were seen in plasma aldosterone concentration, plasma renin activity, or angiotensin-converting enzyme activity between the groups. Administration of CS-866 for six months did not affect either glucose tolerance or insulin sensitivity. Other model parameters such as basal (steady-state) insulin and glucose concentration, first- and second-phase post-hepatic insulin delivery to glucose, and insulin clearance rate constant were unaffected. In conclusion, CS-866 treatment reduced systolic BP without affecting glucose/insulin metabolism under hyperlipidaemic conditions produced by cholesterol feeding.
 ...
PMID:Angiotensin II type-1 receptor antagonist, CS-866, reduces blood pressure without affecting glucose/insulin metabolism in cholesterol-fed rabbits. 1178 97

High neonatal activity of the renin-angiotensin system (RAS) is crucial for the maintenance of glomerular filtration of the newborn. The aim of the present study was to investigate whether genetic polymorphisms leading to lower angiotensin converting enzyme activity (ACE) or impaired functionality of angiotensin II (AII) type 1 receptor (AT1R) might predispose very low birth weight newborns (VLBWs) to the development of acute renal failure (ARF). The medical records of 110 VLBW infants were analyzed. ARF developed in 42 of them during the first postnatal week, while 68 neonates exhibited normal renal function. The ACE I/D polymorphism and the A1166C variants of AT1R were determined from dried blood samples. The frequency of the ACE I allele did not differ in ARF and non-ARF groups (0.307 and 0.284); the frequency of the AT1R C1166 variant was also the same in ARF and non-ARF groups (0.250 and 0.227). Although low activity of RAS has been implicated in the development of neonatal ARF and data indicated that the functionality of RAS is influenced by the I/D variants of the ACE gene and the A1166C variant of the AT1R gene, we could not demonstrate any effect of these polymorphisms on the development of ARF in VLBW infants.
 ...
PMID:Variance of ACE and AT1 receptor gene does not influence the risk of neonatal acute renal failure. 1179 1

Binding of angiotensin II on the angiotensin II type-1 receptor induces cell growth, while triggering via the angiotensin II type-2 (AT(2)) receptor causes an opposing effect of growth inhibition and apoptosis. AT(2) receptor stimulation has also been shown to enhance inducible nitric oxide synthase (iNOS) expression, an enzyme associated with cancer. To study the involvement of the angiotensin II receptors and iNOS in the carcinogenesis of human breast, we visualised both factors in tissues from patients with hyperplasia, ductal carcinoma in situ (DCIS) and invasive carcinoma using immunocytochemistry and in situ hybridisation. In normal ducts, levels for AT(2) protein and mRNA are low, but these are markedly increased in all pathological tissues. While in normal tissue both negative and positive ducts are found, the staining patterns in hyperplasia, DCIS and invasive carcinoma have a homogeneous positive appearance. Similarly, iNOS enzyme expression was very low in the ductal epithelium of normal tissues, but highly increased in all pathologies, with the highest expression found in hyperplastic ducts. Three human cell lines were assayed for the presence of AT(2) receptor. Normal HMec 1001-3 cells were weakly positive, but only one of the adenocarcinoma cell lines, designated SK-BR-3, was shown to express both AT(2) protein and its mRNA. We show that AT(2) receptor and iNOS overexpression are associated with breast disease, further confirming the involvement of the components of the renin-angiotensin system in the aetiology of breast cancer.
 ...
PMID:Increased angiotensin II type-2 receptor density in hyperplasia, DCIS and invasive carcinoma of the breast is paralleled with increased iNOS expression. 1181 93

The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
 ...
PMID:From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis. 1183 7

Many studies have suggested that the renin-angiotensin system plays an important role in the left ventricular (LV) remodeling and cardiac dysfunction that occurs after myocardial infarction (MI). Although angiotensin II type IA (AT1A) receptor knockout (KO) mice are reported to display less LV remodeling after MI, diastolic dysfunction has not been fully evaluated, so the present study measured transmitral inflow pattern in both AT1A receptor KO mice with MI (KO-MI) and wild type mice with MI (WT-MI). Cardiac geometry and function were examined by Doppler echocardiography and myocardial mRNA expression was determined by Northern blot analysis at 4 weeks after MI. The LV internal diastolic dimension of WT-MI was larger than that of the KO-MI (p<0.05). Marked increases in the E wave velocity and the ratio of the peak velocity of the E wave to the A wave were observed in the WT-MI (p<0.01). The deceleration rate of the E wave in KO-MI was lower than in WT-MI (p<0.05). mRNA expressions of ANP, BNP, collagen I and collagen III in the non-infarcted LV and RV of KO-MI were significantly lower than WT-MI. In conclusion, transmitral inflow abnormalities in KO-MI were attenuated compared with WT-MI.
 ...
PMID:Transmitral inflow pattern assessed by Doppler echocardiography in angiotensin II type 1A receptor knockout mice with myocardial infarction. 1199 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>