Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension in various experimental models, including spontaneously hypertensive rats (SHR), is associated with elevated rates of vascular collagen synthesis. The sympathetic nervous system is an important factor in the etiology of hypertension in SHR. The primary purpose of this study was to determine the effects of the alpha 1-adrenergic receptor antagonist doxazosin on aortic collagen synthesis and on systolic arterial pressure in SHR. Doxazosin was administered either short-term (20 or 200 mg/kg/day by gavage over 5 days) or long-term (0.02 or 0.20 g/L in the drinking water over 8 weeks). Rates of collagen synthesis were determined by incubating aortic segments with 14C-proline in vitro and then measuring either the formation of 14C-hydroxyproline by means of high-performance liquid chromatography, or the amount of radioactivity liberated by collagenase digestion. Systolic arterial pressure was monitored with the standard tail-cuff technique. Both doses of doxazosin depressed aortic collagen synthesis at 8 weeks of treatment, but neither dose had any effect at 4 weeks. In the short-term study only the higher acute dose of doxazosin significantly reduced aortic collagen synthesis; the lower dose had no effect. In the short-term study doxazosin reduced systolic arterial pressure, with a maximum effect at 1-2 days. Tolerance to the depressor effect developed over the remaining 3-4 days, especially with the higher dose. In the 8-week study, the lower doxazosin dose had no effect on systolic arterial pressure, and the higher dose exerted a biphasic effect, moderately but significantly reducing systolic arterial pressure at 1 and 8 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1987
PMID:Effects of doxazosin on vascular collagen synthesis, arterial pressure and serum lipids in the spontaneously hypertensive rat. 244 37

We studied whether alpha-human atrial natriuretic peptide (alpha-hANP) had the capacity to regulate cyclic AMP (cAMP) levels in human glomeruli, since decreased cAMP in the glomerulus may increase the glomerular filtration rate (GFR) through increasing kf (glomerular capillary ultrafiltration coefficient). Human kidneys were obtained at surgery for carcinoma. Normal cortical tissues from these kidneys were used for the study. After incubating the renal cortical slices with 0.1% collagenase, glomeruli were dissected manually under the stereomicroscope. Two glomeruli were incubated (37 degrees C, 2 min) with parathyroid hormone (PTH) and/or alpha-hANP. cAMP was determined by radioimmunoassay. alpha-hANP at a concentration of 5 x 10(-6) M had no effect on glomerular cAMP accumulation in the basal condition. PTH stimulated cAMP formation in a dose-dependent manner. alpha-hANP inhibited significantly the increase in cAMP formation induced by PTH (p less than 0.01). This action of alpha-hANP was dose-dependent, with a maximum of 50% inhibition. PTH is one of the endogenous substances that are known to increase cAMP formation and decrease kf. Thus, it seems likely that alpha-hANP increased GFR through modulating the production of cAMP in human kidney.
J Cardiovasc Pharmacol 1989
PMID:Inhibitory effect of human atrial natriuretic peptide on cyclic AMP levels in microdissected human glomeruli. 247 46

Apamin, a bee venom polypeptide, is reported to block the Ca2+-dependent K+ channel in smooth muscle, hepatocyte, and neuroblastoma cells. In embryonic chick hearts, it was found to block the Ca2+ channel. We report here that apamin (10(-9)-10(-7) M) hyperpolarizes the resting membrane potential and shortens the duration of the action potential (AP) in the fast response of adult guinea pig ventricular papillary muscles. This peptide also depresses the isoproterenol or Ba2+-induced slow response APs in the presence of high K+ (21.6 mM) Tyrode solution, without affecting the resting potential. The most striking effect of apamin on the slow response was to shorten the duration of AP with only slight decreases in the maximal rate of increase (Vmax) of the AP, a nonlinear measure of Ca2+ currents. These findings suggest that apamin increases membrane K+ conductance in the mammalian ventricular myocardium. However, in enzymatically isolated single ventricular cells and at wide range of concentrations (10(-7)-10(-11) M), apamin did not affect the AP configuration and did not alter the membrane Ca2+ or K+ current, perhaps because of a loss of apamin sensitivity secondary to enzymatic digestion of the tissue with collagenase.
J Cardiovasc Pharmacol 1989 Jul
PMID:Possible increases in potassium conductance by apamin in mammalian ventricular papillary muscles: a comparison with the effects on enzymatically isolated ventricular cells. 247 13

Analysis of the conditioned medium from cultured human heart valves showed that these tissues secrete a biologically active factor that induces chondrocytes in cultured cartilage to degrade extracellular matrix proteoglycan. This activity was similar to that described for porcine interleukin-1 (catabolin) and a cytokine secreted by cultured porcine heart valves (cardiac catabolic factor). The biological activity of the material in human valve conditioned medium was unaffected by the presence of low doses of cortisol, but its production by cultured valves was impaired by this steroid or benoxaprofen and abolished by cycloheximide. Addition of the conditioned medium to fibroblast monolayers stimulated the secretion of prostaglandin E and the tissue inhibitor of metalloproteinases (TIMP) but not collagenase. Preincubation of the conditioned medium with antiserum raised to the acidic form of porcine interleukin-1 neutralised the proteoglycan degrading stimulus. The material is biologically similar to other cytokines and antigenically related to porcine interleukin-1.
Cardiovasc Res 1987 Jan
PMID:Production of a factor by cultured human heart valves that is immunologically related to interleukin 1. 349 25

Ventricular cells from adult rats were isolated enzymatically and used as a model system for determining what factors affect the release of adenosine triphosphate (ATP) from myocardial cells. The enzyme systems used to isolate cells were trypsin:collagenase; hyaluronidase:collagenase and dispase:collagenase. Adenosine triphosphate was released in greater amounts in response to hypoxia from cells freed by each of the enzymatic procedures. This occurred while the intracellular concentration of ATP remained constant. Experiments were then performed to determine whether the conditions that occur during myocardial ischaemia or hypoxia altered the release of ATP. Cells suspended in either oxygenated or anoxic buffer at a pH of 6.8 released a significantly lower amount of ATP than cells suspended in either condition at pH 7.4. To test the possibility that ATP was released from nucleotide-protein-Ca2+ complexes located in the sarcolemma, artificial disruption of these structures was carried out. Incubation of oxygenated cells with the chelating agent, ethyleneglycol-bis (B-aminoethyl ether)-N, N-tetraacetic acid (EGTA), stimulated the release of ATP in a hyperbolic relationship while incubation of anoxic cells with ethylenediamine tetraacetate (EDTA) stimulated the release of ATP in such a way that the pattern of release followed a sigmoid response with maximal amounts of ATP, 995 +/- 55 pmol.mg-1 protein, occurring in the presence of 0.1 to 2.0 mmol.litre-1 EDTA. By incubating cells with radioactive EDTA, there was no indication that EDTA entered the cells. No release of ATP above control levels occurred when EDTA was chelated with Ca2+ before being applied to isolated cells. These data suggest that the source of ATP found extracellularly may have been nucleotide-protein-Ca2+ complexes located in the sarcolemma, and further support the role of ATP as a coronary vasodilator during hypoxic conditions.
Cardiovasc Res 1983 May
PMID:Possible source of adenosine triphosphate released from rat myocytes in response to hypoxia and acidosis. 641 42

Vascular endothelial cell (EC) wound healing was characterized on an EC-synthesized extracellular matrix (ECM) previously treated with enzymes and antibodies specific for ECM components. Using a computer-assisted video-microscope recording system capable of automatic EC recognition, we learned whether components of the EC-synthesized matrix influenced post-injury migration and wound healing in vitro. Localization of actin and its encoded mRNA using isoform-specific antibodies and labeled cDNA probes allowed for a direct correlation of living-cell behavior with cytoskeletal form and distribution. Results of these studies indicate that the computer-assisted EC tracking system allows for an automatic and reproducible analysis of EC behavior following injury in vitro. EC migrate fastest immediately following injury and then achieve a new, slower migration rate that is maintained until EC from one edge of 200- to 300-microns-wide wound zone contact EC from the other wound face. Treatment of EC-synthesized matrices with antibodies against fibronectin and laminin has no effect on EC migration following injury (-0.25 microns/min) or on cytoskeletal array. Similarly, digestion of these matrices with heparinase and hyaluronidase has no effect on wound healing rates. Slowly spreading EC cytoplasm, which borders the intact and antibody-treated EC matrices, is rich in actin but lacks myosin II. Two different preparations of collagenase (bacterial and mammalian) each potentiate EC wound healing in vitro. Bacterial collagenase treatment of the EC-synthesized matrices potentiates EC migration fivefold (1 micron/min) while treatment of EC-matrices with mammalian cell collagenase stimulates EC migration following injury some twofold (0.4 micron/min) over control values. Whereas EC on control matrices migrate in unison as a tissue-like sheet, EC on the collagenase-treated EC matrices migrate as individuals. Concomitant with the increased rates of migration following injury on the collagenase-treated EC-matrices is a two- to fourfold increase in the steady-state levels of beta-actin mRNA. This increase in actin mRNA abundance is observable by its preferential localization (seen by in situ hybridization) in the lamellae bordering the wound edge in association with beta-actin, which is exclusively localized there. Because beta-actin and its encoded mRNA are positioned together in association with the plasma membrane in regions of moving cytoplasm, it seems likely that beta-actin filament assembly is required for motility following endothelial injury.
J Cardiovasc Pharmacol 1993
PMID:Molecular mechanisms regulating the vascular endothelial cell motile response to injury. 752 70

The clinical course of 76 patients with aortic aneurysmal disease undergoing 107 coincidental surgical procedures was analysed in order to examine the relationship between aortic aneurysmal rupture and coincidental treatment. Additionally the incidence of aneurysmal rupture was assessed following 82 endoscopic procedures in 42 patients with aortic aneurysms. Two patients ruptured an aortic aneurysm after operation, one after colonoscopy (maximal transverse diameter 7 cm) and one after coronary artery bypass grafting (maximal transverse diameter 5.6 cm). The mean maximal transverse diameter of aneurysms in 76 patients was 5.08 cm (95% confidence interval 4.7-5.4 cm). Both patients with ruptured aortic aneurysm were outside these confidence limits and were known hypertensives whose perioperative control of hypertension was questionable. The present series of patients is discussed with reference to induction of collagenase activity as a precipitating cause for postoperative rupture of aortic aneurysms, perioperative control of hypertension, transverse aneurysm diameter as a predictor of postoperative rupture and conduct of coincidental procedures in the presence of aneurysmal disease.
Cardiovasc Surg 1995 Feb
PMID:Incidence of rupture of aortic aneurysms after coincidental operation. 778 Jul 5

Previous studies in the authors' laboratory have demonstrated that degradation of arterial elastin produces vessel dilatation, decreased vessel distensibility, and vessel elongation which can cause tortuosity. By contrast, degradation of collagen produces increased vessel distensibility and rupture. However, neither degradation of elastin nor of collagen produced the true gross enlargement characteristic of human aneurysms. The present study was performed to identify the connective tissue critical to aneurysm formation. Vessel dimensions were measured repeatedly in human arteries during progressive enzymatic degradation. Experiments were performed on six intact human common, external and internal iliac arteries, and two aneurysmal human common iliac arteries. The vessels were mounted in vitro and subjected to pressure steps up to 200 mmHg while diameters were measured. Repeated pressure-diameter curves were obtained for up to 18 h during treatment with elastase or collagenase. Degradation of elastin produced moderate dilatation (6-10% at 100 mmHg) with decreased vessel distensibility; this occurred as the load was shifted to remaining collagen. Degradation of collagen produced greater dilatation (10-23% at 100 mmHg), increased distensibility, and vessel rupture. These findings suggest that the critical element in both the gross enlargement and rupture of aneurysms resides in collagen. They also suggest that, in vessels obtained from patients with a family history of aneurysms, defects should be sought in: (i) the structure of collagen; (ii) increased susceptibility of collagen to degradation by endogenous mechanisms; (iii) increased endogenous collagenolytic activity; or (iv) decreased inhibition of endogenous collagenolytic activities.
Cardiovasc Surg 1994 Aug
PMID:Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation. 795 54

A complete technique is described for the isolation of myocytes from mammalian hearts using the Langendorff perfusion technique. The use of calcium-free solution containing collagenase and protease, followed by low calcium solution, consistently results in a large number of calcium tolerant myocytes which are well suited for long periods of electrophysiological recording.
Cardiovasc Res 1994 Feb
PMID:How to isolate cardiac myocytes. 814 11

In this study, we evaluated cardiac myocyte viability and function under hypothermic conditions with four types of storage solutions, saline solution, Euro-Collins solution, University of Wisconsin solution, and MCDB 107 medium. Cardiac myocytes were isolated from neonatal rat ventricles by collagenase dispersion and cultured for 4 days with MCDB 107 medium. A total of 12.5 x 10(5) myocytes per culture dish was used and the myocytes were incubated at 4 degrees C for 6, 12, 18, and 24 hours in the various storage solutions. After each incubation time, creatine kinase and lactate dehydrogenase were measured in the storage solutions. The myocytes were then incubated for 24 hours at 37 degrees C to evaluate the recovery of the myocyte beating rate. In the MCDB 107 group (n = 7), the recovery ratio of myocyte beating rate was complete by 12 hours, then decreased to 44.8% of control (beating rate before hypothermic incubation) at 24 hours. The saline, Euro-Collins, and University of Wisconsin groups (n = 7 each) had significantly lower recovery ratios than the MCDB 107 group (at 12 hours: 61.0%, 32.2%, and 48.9%; at 18 hours: 0.0%, 5.5%, and 15.1% of control, respectively). Release of creatine kinase and lactate dehydrogenase in the MCDB 107 group gradually increased and at 24 hours was 143.2 mIU/flask and 486.2 mIU/flask, respectively. However, the saline and University of Wisconsin groups had significantly increased creatine kinase and lactate dehydrogenase values at 24 hours (creatine kinase: 334.6 and 319.6 mIU/flask; lactate dehydrogenase: 821.6 and 654.4 mIU/flask, respectively). The Euro-Collins group showed the greatest increase in both markers (creatine kinase: 1587.5, lactate dehydrogenase: 2106.9 mIU/flask). In summary, saline and University of Wisconsin solutions showed a beneficial effect on recovery of myocyte viability at 12 hours compared with Euro-Collins solution, however MCDB 107 medium had the best overall protective effect on cultured myocytes. Accordingly, alternate hypothermic storage solutions, such as cell-culture medium, may have protective characteristics that are suitable for cardiac preservation.
J Thorac Cardiovasc Surg 1994 Jan
PMID:Cardiac myocyte functional and biochemical changes after hypothermic preservation in vitro. Protective effects of storage solutions. 828 90


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