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)

The function of the renin-angiotensin-aldosterone system (RAAS) in the mammalian eye remains unclear, although alterations in the concentrations of various pathway components can influence intraocular pressure and the electroretinogram. Angiotensin Converting Enzyme (ACE) has been localized to ocular tissues and fluids. Aqueous humor and serum values of ACE are increased in sarcoid uveitis patients. We used the dog to simultaneously examine the effects of a topically administered ACE inhibitor on the intraocular pressure (IOP), on components of the renin-angiotensin pathway in the serum and aqueous humor, and to monitor any systemic effects of the ACE inhibitor. The novel ACE inhibitor, SCH 33861 (Schering Corporation), decreased IOP in amounts similar to timolol when applied topically to the canine eye. Serum ACE values significantly decreased in SCH 33861 treated dogs, while aqueous ACE values were only slightly decreased. A decrease in heart rate, and systolic and diastolic blood pressure in these dogs during the treatment period indicated probable systemic absorption. Normal values of aqueous humor and serum angiotensin-I were established for the dog. Plasma renin activity and angiotensin-I values were not significantly changed for any of the treatment groups. Topical application of SCH 33861 to the canine eye is a useful model to further evaluate the role of the renin-angiotensin system in the eye.
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PMID:Angiotensin converting enzyme system in the normal canine eye: pharmacological and physiological aspects. 164 19

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lenticular rubidium uptake and plasma renin activity in weanling cataract-prone salt-sensitive rats. 240 57

Angiotensin-II, the most important biologically active product of the renin-angiotensin system, has been reported to play a role in neovascularization, and prorenin has been found in the vitreous of human eyes, particularly in those affected by proliferative diabetic retinopathy, a disease characterized by neovascularization. The prorenin level in these eyes was, relative to that of plasma albumin, higher than in eyes without neovascularization. These findings suggested that an intraocular renin-angiotensin system exists, which might be involved in the development of retinal neovascularization in diabetes mellitus. In this study angiotensin-I-generating activity was measured in bovine aqueous humor and vitreous and in extracts of bovine retina, pigment epithelium-choroid, and anterior uveal tract before and after subjecting these extracts to procedures known to convert prorenin to renin. The measurements were made by incubation at 37 C with plasma from nephrectomized rats at pH ranging from 5.0-8.5. True renin in the ocular samples could be separated from nonrenin acid protease by alpha-casein-Sepharose affinity column chromatography at pH 3.5; true renin did not bind to the column, whereas acid protease did. True renin was further identified by its relatively high pH optimum (6.5-7.0) for angiotensin-I generation, its complete inhibition with specific renin antiserum, and its high affinity for specific renin inhibitors. More than 75% of angiotensin-I-generating activity of the ocular samples consisted of true renin. Approximately 90% or more of total renin (renin plus prorenin) in aqueous humor, vitreous, and ocular tissue could not be explained by trapped plasma. Total renin in aqueous humor and renin in vitreous were near the detection limit of the assay of angiotensin-I-generating activity. In vitreous prorenin comprised 99% of the total renin, in retina 81%, and in pigment epithelium-choroid and anterior uveal tract less than 50%. Prorenin in ocular fluids showed a concentration gradient, posterior vitreous greater than anterior vitreous greater than aqueous humor, suggesting that the main source of extracellular prorenin was in the posterior eye. These data support the contention of local renin and/or prorenin synthesis in the eye and are in accordance with the observations in other tissues that extrarenal synthesis of renin is often associated with the release of mainly, or exclusively, prorenin into extracellular fluid.
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PMID:Identification and quantification of renin and prorenin in the bovine eye. 240 20

The presence of constituents of the renin-angiotensin system (RAS) in ocular tissues and fluids suggests this system is involved in ocular physiology. Angiotensin II (AngII) is the main biological effector of the system, so we measured AngII in plasma and in aqueous humor of the anterior ocular chamber of patients undergoing cataract extraction. Untreated normotensive patients were compared with arterial hypertensive patients taking either diuretics which stimulate the RAS or angiotensin converting enzyme (ACE) inhibitors which reduce the production of AngII. Plasma levels of AngII were higher in patients on diuretics (5.46 +/- 1.04 fmol/ml; mean +/- SEM) than in untreated cataract patients (2.28 +/- 0.32 fmol/ml, p < 0.02), and were very low with ACE inhibitors (0.51 +/- 0.18 fmol/ml). In aqueous humor, AngII was measurable in 7 of 11 patients on diuretics (median 1.1 fmol/ml), and in 6 of 16 normotensive patients (median < 0.55 fmol/ml), but not in aqueous humor of 4 patients receiving enalapril or captopril. These results demonstrate the presence of AngII in the eye but do not exclude either its sequestration in the eye or local production. The possibility of individual measurements of intraocular AngII will permit more precise determination of its role in future studies.
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PMID:Individual measurements of angiotensin II concentrations in aqueous humor of the eye. 771 76

Asymmetric dimethylarginine (ADMA) is an endogenous NO synthase (NOS) inhibitor whose production is enhanced by oxidative stress. Recent studies have shown that ADMA may also directly stimulate the production of reactive oxygen species (ROS) by up-regulation of the renin-angiotensin system independently of NOS inhibition. In this study, to investigate the clinical association of ADMA with diabetic retinopathy, we evaluated the levels of ADMA and NO oxides (NO2- and NO3-) in serum and aqueous humor obtained during cataract surgery from non-diabetic subjects (n = 21) and diabetic patients (n = 17). We found that the ADMA existed in aqueous humor and its level was similar to that in serum. The ADMA levels in both serum and aqueous humor were higher in diabetic patients, especially those with severe retinopathy, than in the non-diabetic group (serum ADMA: 0.67 +/- 0.26 vs. 0.53 +/- 0.08 micromol/l, p<0.05; aqueous humor ADMA: 0.55 +/- 0.20 vs. 0.32 +/- 0.16 micromol/l, p<0.05). Also, the aqueous humor level of ADMA, but not the serum level, was correlated with HbA1c on analysis of all the patients (R = 0.33, p<0.05 by simple regression analysis). However, a correlation between the ADMA levels in serum and aqueous humor was not observed in either the non-diabetic group or the diabetic group. Furthermore, serum and aqueous humor levels of NOx did not differ between the two groups, and no correlation with ADMA levels was observed in either group. These results suggest that ROS production may be enhanced in the eyes of diabetics. Since ADMA may act to potentiate ROS production independently of its inhibition of NOS, further investigation is required to clarify the possible contribution of ADMA to the development or progression of retinopathy.
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PMID:Asymmetric dimethylarginine (ADMA) in the aqueous humor of diabetic patients. 1737 59

The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is present e.g. in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.
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PMID:Many Faces of Renin-angiotensin System - Focus on Eye. 2876 66