Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MK-422 (enalaprilat) (0.0005-0.5%) significantly reduced intraocular pressure (IOP) in African Green monkeys. Studies utilizing unilateral instillation of MK-422 and its inactive R-isomer indicated a local site of action within the eye which is dependent upon inhibition of angiotensin converting enzyme, also known as kininase II. Tonography showed a small increase (21%) in conventional aqueous humor outflow facility which did not entirely account for the IOP lowering effect of MK-422. Pretreatment with indomethacin or pilocarpine specifically attenuated the ability of MK-422 to lower IOP suggesting that biosynthesis of prostaglandins and uveoscleral outflow pathways are important in mediating the ocular hypotension. The data indicate that MK-422 may lower IOP in monkeys by virtue of its ability to prevent the breakdown of bradykinin and thereby promote the formation of endogenous prostaglandins in the eye.
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PMID:Prostaglandins mediate the ocular hypotensive action of the angiotensin converting enzyme inhibitor MK-422 (enalaprilat) in African green monkeys. 216 28

Inhibitors of angiotensin converting enzyme (ACE) (1) and of carbonic anhydrase (CA) (2,3) decrease intraocular pressure (IOP) in conscious rabbits. We asked whether ACE inhibition decreases IOP through effects on CA-dependent flow of aqueous humor (AH) and whether ACE inhibitors decrease other CA-dependent secretions. We show in anesthetized rabbits (a) that topical inhibitors of ACE decrease both IOP and AH flow as much as systemic inhibitors of CA; (b) that the maximal effects of ACE and CA inhibition are not additive, therefore these treatments may affect one or more components of a single system for fluid production; and that (c) ACE inhibitors do not work through inhibition of CA. Looking at other fluid production systems, we find (d) that cerebrospinal fluid (CSF) production is increased after ventriculocisternal perfusion with a potent ACE inhibitor and (e) that flow of pancreatic juice (PJ) is increased after systemic ACE inhibition.
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PMID:Effects of inhibition of angiotensin converting enzyme and carbonic anhydrase on fluid production by ciliary process, choroid plexus, and pancreas. 269 32

We studied the effects of a new topical angiotensin converting enzyme inhibitor, SCH 33861, in lowering intraocular pressure in 20 patients with ocular hypertension or primary open-angle glaucoma. In a double-masked, four-way crossover study with placebo and timolol, SCH 33861 was well tolerated and effective in lowering intraocular pressure. The magnitude of the drug's effect in lowering intraocular pressure was less than that of timolol 0.5%.
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PMID:Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open-angle glaucoma. 328 43

SCH 33861 is a novel, non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor. Topical administration of the compound to the eye of conscious rabbits was employed to examine actions on intraocular pressure (IOP). Falls in IOP resulted from SCH 33861 (0.001-0.01%) administration. Ocular hypotensive responses were sustained for as long as 24 hrs following a single application of 0.001% SCH 33861. The RSS isomer of SCH 33861, which is 200-fold weaker an ACE inhibitor than SCH 33861, caused only transient falls in IOP at 0.1% concentration. The magnitude of the fall in IOP induced by 0.001% SCH 33861 (4.8 +/- 0.5 mmHg) was comparable to that produced by 0.5% timolol (4.5 +/- 0.3 mmHg). Other ACE inhibitors such as captopril (0.1%) and enalaprilic acid (0.01%) also reduced IOP by 4.0 +/- 0.4 and 4.7 +/- 0.4 mmHg, respectively. These findings indicate that SCH 33861 is 500-fold more potent on a weight basis than is timolol in lowering IOP. No loss of ocular hypotensive activity was observed when SCH 33861 was administered twice daily for 5 days suggesting little, if any, potential for tolerance development. SCH 33861, as well as the other ACE inhibitors, caused neither ocular irritation nor alteration of pupil diameter. These findings suggest that inhibition of ocular ACE may represent an effective means of reducing IOP.
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PMID:Topical ocular hypotensive effects of the novel angiotensin converting enzyme inhibitor SCH 33861 in conscious rabbits. 350 19

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound.
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PMID:Effect of oral captopril (SQ 14225) on intraocular pressure in man. 779 97

Quantum chemical QSAR expressions have been developed for a heterogeneous group of 36 sulfonamides which have been shown to lower intraocular pressure in in vivo tests on animals. It was found, using the ACE statistical technique, that the lowering of intraocular pressure correlated non-linearly with K(I) for carbonic anhydrase inhibition and with solubility. Non-linear transformations had to be applied to both the response variable and to solubility. Chemical variables found to be relevant to CA inhibition included the dipole moment vector, the frontier orbital energies, the solvation energy determined by the COSMO model, the electrostatic potential based charges on the atoms of the sulfonamide group, and the size and polarizability of the molecule.
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PMID:Carbonic anhydrase inhibitors. Part 86. A QSAR study on some sulfonamide drugs which lower intra-ocular pressure, using the ACE non-linear statistical method. 1100 87

Therapeutic methods directed at alleviating the basic pathological processes of normal-tension glaucoma (NTG) are yet to be established. Although there seems to be little doubt that intraocular pressure (IOP) represents a risk factor in most patients, reduction of IOP does not prevent progression in every patient with NTG, indicating that factors other than elevated IOP are involved in glaucoma progression. New avenues of treatment under investigation include agents that could improve blood flow to the eye and neuroprotective drugs. The major components of the renin-angiotensin system have been identified in ocular tissue. Angiotensin-converting enzyme (ACE) inhibitors are widely used to treat systemic hypertension. ACE inhibitors are inhibitors of kininase II and thus prevent breakdown of bradykinin. Bradykinin displays protective actions against glutamate neurotoxicity through bradykinin-B(2) receptors in cultured retinal neurons. ACE inhibitors blocked the liberation of angiotensin II from angiotensin I. Lower angiotensin II levels may have beneficial effects on outcomes by lowering vascular superoxide anion production. The effects of ACE inhibitor as a potential antiglaucoma therapy deserve intense scrutiny.
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PMID:Potential role for angiotensin-converting enzyme inhibitors in the treatment of glaucoma. 1966 75

The angiotensin converting enzyme (ACE), which is responsible for the conversion of angiotensin-I to angiotensin-II, and metabolism of bradykinin is found to be present in human ocular tissue and it manifests a variety of physiological and pharmacological effects. Angiotensin increased the intraocular pressure (IOP) in animals. Even, the topical instillation of ACE inhibitors have been reported to reduce the IOP in rabbits. We, therefore performed this randomized, double masked, parallel groups-design and placebo controlled study, to investigate the acute effect of captopril (6.25 mg, 12.50 mg, and 25.00 mg) and placebo on IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate in healthy human volunteers. These parameters were monitored for 4.0 h after the administration of drugs. Captopril 12.50 mg and 25.00 mg significantly reduced the IOP and SBP (P < 0.05). Captopril 6.25 mg also had a tendency to lower the IOP and significantly decreased the SBP (P < 0.05). The mechanism involved in the decrease of IOP and blood pressure with captopril could be due to inhibition in the formation of angiotensin-II and sparing of bradykinin.
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PMID:SHORT-TERM EFFECT OF CAPTOPRIL ON INTRAOCULAR PRESSURE. 2709 44

The renin-angiotensin system (RAS) is one of the oldest and most extensively studied human peptide cascades, well-known for its role in regulating blood pressure. When aldosterone is included, RAAS is involved also in fluid and electrolyte homeostasis. There are two main axes of RAAS: (1) Angiotensin (1-7), angiotensin converting enzyme 2 and Mas receptor (ACE2-Ang(1-7)-MasR), (2) Angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor (ACE1-AngII-AT1R). In its entirety, RAAS comprises dozens of angiotensin peptides, peptidases and seven receptors. The first mentioned axis is known to counterbalance the deleterious effects of the latter axis. In addition to the systemic RAAS, tissue-specific regulatory systems have been described in various organs, evidence that RAAS is both an endocrine and an autocrine system. These local regulatory systems, such as the one present in the vascular endothelium, are responsible for long-term regional changes. A local RAAS and its components have been detected in many structures of the human eye. This review focuses on the local ocular RAAS in the anterior part of the eye, its possible role in aqueous humour dynamics and intraocular pressure as well as RAAS as a potential target for anti-glaucomatous drugs.KEY MESSAGESComponents of renin-angiotensin-aldosterone system have been detected in different structures of the human eye, introducing the concept of a local intraocular renin-angiotensin-aldosterone system (RAAS).Evidence is accumulating that the local ocular RAAS is involved in aqueous humour dynamics, regulation of intraocular pressure, neuroprotection and ocular pathology making components of RAAS attractive candidates when developing new effective ways to treat glaucoma.
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PMID:Local ocular renin-angiotensin-aldosterone system: any connection with intraocular pressure? A comprehensive review. 3230 46