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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.
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PMID:[Enzymatic ocular hypertension: a statistical study (author's transl)]. 14 59

The injection of alpha-chymotrypsin into the posterior chamber of the eye is known to produce an experimental ocular hypertension of long duration in animals. The present study reports the pathological changes which occur in the eye during the first nine months after the ocular injection of alpha-chymotrypsin in rabbits. Six weeks after treatment most of the eyes showed a buphthalmia and an intraocular pressure elevation which varied greatly from animal to animal. The anterior chamber angle of the treated eyes showed a progressive enlargement. Several days after the enzyme injection a transient increase in thickness of the cornea and Descemet membrane was noted. Cupping of the optic disc, characterized by a total disappearance of the optic nerve head fibers and an excavation beginning at margins of the retina appeared after four months and in most cases were present seven months after the treatment. More or less prominent retinal degeneration was also evidenced three months after enzyme injection. The results indicate alpha-chymotrypsin-induced occular hypertension in the rabbit leads after several months to pathological change in the eye analogous to that observed in human glaucoma.
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PMID:[Experimental alpha-chymotrypsin model of glaucoma in the rabbit: histopathological studies (author's transl)]. 52 8

There are many unanswered questions about chronic glaucoma which cannot be investigated in the available animal models. The present experiments were designed to develop a rabbit model of chronic intraocular hypertension with characteristics similar to human chronic glaucoma by ligating vortex veins or by making single or multiple intraocular injections of 0.5% or 1% alpha-chymotrypsin, 20% chondroitin sulphate, 2% hydroxypropyl methylcellulose, 2% sodium carboxymethylcellulose or 1% or 2% methylcellulose. Evaluation was based on the clinical findings, intraocular pressure and the retrograde axoplasmic transport function of the optic nerve using a horseradish peroxidase histochemical technique. Most methods either failed to produce moderate chronic intraocular hypertension or were associated with other complications. However, a reliable and relatively long period (eight weeks) of intraocular hypertension was developed by a series of four intra-anterior chamber injections of 1% or 2% methylcellulose. This model has been proved suitable for the study of structural and functional damage to the retina and optic nerve caused by chronic glaucoma.
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PMID:Development of experimental chronic intraocular hypertension in the rabbit. 144 75

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.
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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.
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PMID:Treatment of pain in chronic pancreatitis by inhibition of pancreatic secretion with octreotide. 769 8

Cultures of vascular smooth muscle cells (VSMC) are commonly used to study the events and defects found in hypertension and atherosclerosis. In particular Ca2+ homeostasis in cellular signalling has been the focus of extensive research. Since trypsin has been shown to mobilise Ca2+ in some cell types, we have investigated its effect on various aspects of Ca2+ homeostasis in rat aortic smooth muscle cells (RASMC). The effects of trypsin, alpha-chymotrypsin and elastase (other serine proteases) on intracellular Ca2+ in cultured aortic cells isolated from Wistar rats have been investigated. Trypsin (24 micrograms/ml) elicits intracellular Ca2+ mobilisation, after which cells become nonresponsive to thrombin Ca2+ mobilisation but retain responsiveness to Angiotensin II (AII). alpha-Chymotrypsin (24 micrograms/m) inhibits the thrombin Ca2+ mobilising response, without itself initiating a Ca2+ transient or affecting AII Ca2+ mobilisation. Elastase (24 micrograms/ml) was not effective in mobilising intracellular Ca2+ or inhibiting the thrombin response. We have also observed diminished thrombin Ca2+ mobilisation responses between cells in suspension and cell monolayers, which appeared to be unrelated to proteolysis but due to morphological changes of the cells. Our results suggest that trypsin acts on the thrombin receptor via a specific proteolysis mechanism to mobilise intracellular Ca2+ ([Ca2+]i) in RASMC. The amount of Ca2+ released by thrombin or trypsin is dependent on the morphology of the cell and the state of the tethered ligand of the thrombin receptor exposed by the protease.
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PMID:The effect of thrombin and serine proteases on intracellular Ca2+ in rat aortic smooth muscle cells. 779 84


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