Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors have carried out a statistical study on two large groups of patients operated on for cataract and in whom the enzyme alph-chymotrypsin has been used, and the occurrence of ocular hypertension has been examined. One group, which contained 1,003 operations most of which were under the microscope using a firm closure technique, was compared with another group of 324 cases operated under the same conditions but without using the enzyme. In all cases the intraocular pressure was measured 24-48 hours after the operation. The rise in pressure, the rapidity of its development were studied together with its duration and the concentration of the enzyme. In addition these findings were compared with another group of 2,334 eyes operated on several years previously with standard techniques using a less hermetic wound suture, without a microscope, with alpha-chymotrypsin, but whose tensions were controlled from the third week. The results show conclusively that there is a greater frequency of the occurrence of raised intra-ocular pressure when the enzyme is used (40,3%) than when it is not used (25,3%). This ocular hypertension persists in all cases to the end of three weeks. The time of the appearance of the hypertension, the numbers affected and the duration of the intraocular pressure were not significantly meaningful in the statistical analysis.
 ...
PMID:[Enzymatic ocular hypertension: a statistical study (author's transl)]. 14 59

A newly synthesized orally active renin inhibitor, N-morpholinoacetyl-(1-naphthyl)-L-alanyl-(4-thiazolyl)-L-alanyl (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoyl-n-hexylamide (ES-8891), was found to be a highly potent competitive inhibitor of human renin with an inhibition constant of 1.1 nM. This inhibitor was also active against monkey renin, although there was less inhibition of renin in pig, rabbit, and rat. ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. A single oral administration of ES-8891 (10 or 30 mg/kg) to conscious, sodium-depleted marmosets caused a dose-related decrease in plasma renin activity and blood pressure. ES-8891 (30 mg/kg) produced an 80% inhibition of plasma renin activity, which lasted for more than 6 hours. Kidney renin messenger RNA was not significantly changed 6 hours after oral administration of ES-8891 (30 mg/kg). A single oral administration of 240 mg ES-8891 to healthy human volunteers (n = 6) produced a significant inhibition of plasma renin activity (75% inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) with a good correlation of plasma levels of ES-8891. There were no significant changes in blood pressure or heart rate, and no adverse effects were observed. These results suggest that ES-8891 is an orally active human renin inhibitor that may be clinically useful.
Hypertension 1990 Jun
PMID:ES-8891, an orally active inhibitor of human renin. 211 12

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.
Hypertension 1986 Jun
PMID:Statine-containing dipeptide and tripeptide inhibitors of human renin. 308 74

An orally active renin inhibitor, ES 6864 (N-[(2R)-3-morpholinocarbonyl-2-(1-naphthylmethyl)propionyl]-(4- thiazolyl)-L-alanyl-cyclostatine-(2-morpholinoethyl)amide), was synthesized. ES 6864 was found to be a highly potent inhibitor of human renin with a Ki value of 7.3 x 10(-9) M. The compound competitively inhibited human renin. The inhibitor was also potent against monkey renin but was less effective against renins from pig, goat, dog, rabbit, and rat. ES 6864 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. ES 6864 was resistant to proteolytic actions of the enzymes in rat tissue homogenates (liver, kidney, pancreas, and small intestine). Oral administration of ES 6864 at 30 mg/kg to conscious, sodium-depleted marmosets produced a significant blood pressure reduction and almost complete inhibition of plasma renin activity, which persisted for 5 hours. Oral administration of ES 6864 also produced dose-related decreases of blood pressure in hog renin-infused rats, but the duration of action was much shorter than that in conscious marmosets. The parent compound in the blood following oral administration of ES 6864 to marmosets was confirmed directly by measuring the plasma concentration of ES 6864. These results enhance the possibility of developing renin inhibitors that can be used clinically.
Hypertension 1988 Jun
PMID:A highly potent and long-acting oral inhibitor of human renin. 313 6

We have designed a novel class of potent (0.3-7 nM) renin inhibitors which contain a dihydroxyethylene replacement for what is formally the Leu10-Val11 amide bond. Good potency (0.6 nM), water solubility (greater than 10 mg/ml at 37 degrees C), stability toward degradation by chymotrypsin (t1/2 = 820 min), and in vivo activity in a primate model (15% drop in mean arterial pressure in association with complete inhibition of plasma renin activity) are properties which have been incorporated into compound 10, an interesting new agent to be used in the study of hypertension.
 ...
PMID:Renin inhibitors. Improvements in the stability and biological activity of small peptides containing novel Leu-Val replacements. 328 Mar 45

Plasma from Dahl rats susceptible to salt-induced hypertension (Dahl S rats) contains inhibitory factors that reduce the release of thromboxane A2 from thrombin-activated platelets. Platelet-rich plasma from Dahl S rats on either low salt (0.11 or 0.3% NaCl) or high salt (4% NaCl) diets released about 50% less thromboxane A2 than comparable plasma from Dahl rats that are resistant to hypertension (Dahl R rats). This inhibitory activity was present even in the blood of 4-week-old completely normotensive Dahl S rats on a diet containing 0.11% low NaCl. The inhibitory activity could be transmitted to platelets of normal Sprague-Dawley rats by incubating these platelets in boiled and dialyzed plasma from Dahl S rats. Moreover, the inhibitory activity could be completely washed off the Dahl S platelets by incubation in Dahl R plasma. Thus, Dahl S plasma contains inhibitory factors that reduce platelet thromboxane A2 release. The factors are found in low concentrations even in Dahl R plasma; and in Dahl S or Dahl R plasma the factors are increased 25 to 32% by a 4% high NaCl diet. Digestion of Dahl S and Dahl R plasma with either trypsin or chymotrypsin destroyed the inhibitory factors, which have a molecular weight between 2,000 and 3,500. Twenty-four hours after bilateral nephrectomy, dialyzed plasma from both Dahl S and Dahl R rats was completely devoid of thromboxane A2 inhibitory activity. Thus, the factors appear to be heat-stable polypeptides either produced in the kidney or greatly influenced by the presence of renal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Jun
PMID:Platelet thromboxane inhibition by plasma polypeptides in prehypertensive Dahl rats. 372 57

It has been suggested that pancreatic ductal hypertension, secondary to pancreatic outflow obstruction, is a cause of pain in chronic pancreatitis. This study investigated the effect of inhibiting pancreatic secretion with octreotide in chronic pancreatitis pain. Ten patients with chronic alcoholic pancreatitis and severe daily pain were included in an intraindividual double blind crossover study. All patients received octreotide (3 x 100 micrograms/day subcutaneously) and placebo (3 x 0.9% saline solution subcutaneously) for three days at random. Between both treatment phases a two day washout period was interposed. Intensity of pain (visual analogue scale) and analgesic consumption were carefully registered. Pancreatic secretion was monitored daily by measuring faecal chymotrypsin concentration. It was found that during the administration of octreotide, pancreatic secretion was strongly inhibited (faecal chymotrypsin mean (SD) 1.7 (0.6) U/g) with respect to placebo (9.6 (4.2) U/g) and washout (7.6 (3.1) U/g) periods (p < 0.001). Pain score (29.6 (4.5) v 28.7 (5.8)) and consumption of analgesics were no different during the octreotide and placebo periods. It is concluded that short term inhibition of pancreatic secretion does not result in pain relief in patients with chronic pancreatitis. This finding is in contrast with the hypothesis that outflow obstruction of pancreatic secretion with consequent ductal hypertension is an important cause of severe persistent pain in chronic pancreatitis.
 ...
PMID:Treatment of pain in chronic pancreatitis by inhibition of pancreatic secretion with octreotide. 769 8

Controlled-release buccoadhesive tablets containing pindolol were prepared and evaluated in order to achieve constant plasma concentrations during the treatment of chronic hypertension and to improve the bioavailability of pindolol by the avoidance of hepatic first-pass metabolism. The formulations were tested for weight, hardness, friability, content uniformity, swelling rate, bioadhesive force, and drug release rate values. Carbopol 934 and NaCMC were used as bioadhesive polymers and Methocel K4M, Methocel K15M, and HPC were added as matrix-forming polymers.
 ...
PMID:Development and in vitro evaluation of a buccoadhesive pindolol tablet formulation. 987 86

Recombinant human alpha s1-casein expressed in Escherichia coli was purified and digested with trypsin in an attempt to find peptides with angiotensin-I-converting enzyme (ACE) inhibitory activity. Three novel ACE inhibitory peptides, A-II, B-II and C, were isolated and their amino acid sequences identified as Tyr-Pro-Glu-Arg (residues 8-11), Tyr-Tyr-Pro-Gln-Ile-Met-Gln-Tyr (residues 136-143) and Asn-Asn-Val-Met-Leu-Gln-Trp (residues 164-170) respectively. ACE inhibitory activities were measured for the corresponding synthetic peptides, and the ACE IC50 (the amount of peptide causing 50% inhibition of ACE activity) values of A-II, B-II and C estimated to be 132.5, 24.8 and 41.0 mumol/l respectively. Peptides A-II and C were resistant to further digestion by pepsin, whereas peptide B-II was hydrolysed. All three peptides were resistant to digestion by chymotrypsin. These ACE inhibitory peptides may prove useful for oral administration in the treatment of hypertension.
 ...
PMID:Novel angiotensin-I-converting enzyme inhibitory peptides derived from recombinant human alpha s1-casein expressed in Escherichia coli. 1048 81

Peptides inhibiting angiotensin-I converting enzyme (ACE, EC. 3.4.15.1) are possible cures of hypertension. Food-derived ACE-inhibitory peptides are particularly attractive because of reduced side effects. Previously, we reported ACE-inhibitory activity of grass carp protein hydrolysates. In this work, we report steps for purifying the ACE-inhibitory peptide from the hydrolysate and its biochemical properties. Following steps of ultrafiltration, macroporous adsorption resin, and two steps of reversed phase high performance liquid chromatography (RE-HPLC), a single Val-Ala-Pro (VAP) tripeptide was identified. The tripeptide with excellent ACE-inhibitory activity (IC(50) value of 0.00534 mg/mL) was a competitive ACE inhibitor and stable against both ACE and gastrointestinal enzymes of pepsin and chymotrypsin. This is the first report of food-derived VAP. The identified unique biochemical properties of VAP may enable the application of grass carp protein hydrolysates as a functional food for treatments of hypertension. The developed purification conditions also allow the production of VAP for pharmaceutical applications.
 ...
PMID:Purification and characterization of a novel angiotensin-I converting enzyme (ACE) inhibitory peptide derived from enzymatic hydrolysate of grass carp protein. 2210 May 19


1 2 3 Next >>