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

A sixty-eight-year-old female with bone metastases from gastric cancer successfully treated with induced hypertension chemotherapy using cisplatin is reported. She had undergone R2 curative subtotal gastrectomy in June 1985, and had orally taken tegafur 600 mg/day and then changed to doxifluridine 800 mg/day as postoperative adjuvant chemotherapy. Five months after the operation she had back pains and both 99mTc-MDP and 67Ga-citrate scintigram showed L1 vertebra and rib bone metastasis. Induced hypertension chemotherapy using cisplatin was then intermittently performed from January 1986 to September 1990, a single course of which was 25 mg/body div x 2/week for serial 4 weeks; a total of seven courses were carried out and consequently the total volume of the administered cisplatin reached 1,100 mg. Neither medullar nor renal toxicities were observed, but mild gastrointestinal symptoms were noted. The patient no longer has back pains, and no signs of bone metastases were seen on both scintigrams for two years and eight months from December 1988 to August 1991. This case is very rare because her bone metastases were successfully treated with induced hypertension chemotherapy using cisplatin. However, metastatic bone tumors from gastric cancer usually resist any treatments. It is expected that the successfully treated patients even with bone metastasis will be increasingly reported from now as various new approaches including induced hypertension chemotherapy are introduced.
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PMID:[A case of gastric cancer with recurrent bone metastases successfully treated with induced hypertension chemotherapy using cisplatin]. 138 79

Advances in biomedical technology have contributed effectively to the resolution of basic and clinical problems in Nephrology. Most of our insights on glomerular diseases come from animal models. Antibodies against components of the extracellular matrix have been shown to induce glomerular changes in vivo and the non-collagenous NC1 domain of type IV collagen has been demonstrated to contain the Goodpasture antigen. New pathogenetic mechanisms of glomerular injury are suggested by studies on the interaction of antibodies with glomerular cell surface antigens. Gp330, a glycoprotein expressed at the surface of glomerular visceral epithelial cells, has been recognized to be the most relevant antigen of Heymann nephritis. Antibodies able to crosslink gp330 bind to the antigen at the base of foot processes and the resulting immune complexes are shed into the subepithelial space where they form electron dense deposits. The complement membrane attack complex (C5b-9) is likely to be directly responsible for epithelial cell injury and proteinuria in this model. Other cell surface antigens of the glomerular capillary wall, such as dipeptidyl dipeptidase IV, podocalyxin, podoendin, have been characterized. A novel model of glomerular injury comes from the demonstration that a non-complement fixing monoclonal antibody to a surface sialo-glycoprotein (SGP-115/107) binds to glomerular visceral epithelial cells and causes morphological changes which appear epitope-specific and complement and leukocyte-independent. The mechanisms responsible for the progression of renal disease to glomerular sclerosis have been extensively explored in the last years. Among the hemodynamic factors intraglomerular hypertension has been established to play an important part, at least in some models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Nephrology]. 269 52

The most sensitive nonradiometric routine assay for angiotensin-converting enzyme (ACE) activity uses fluorometry to detect His-Leu released from Hip-His-Leu. Our results indicate that, in contrast to human serum, rat serum and plasma contain large and variable amounts of dipeptidase activity that lead to a subestimation of the ACE activity measured in 0.1 M potassium phosphate buffer, pH 8.3, containing 0.3 M NaCl, the most commonly used assay for human serum and tissue ACE. We describe and validate an assay for 1 to 10 microL rat and human serum or plasma using 5 mM Hip-His-Leu in 500 microL of 0.4 M sodium borate buffer, pH 8.3, containing 0.9 M NaC1 at 37 degrees C that reduced the subestimation error to less than or equal to 3% (rat serum) and less than or equal to 0.1% (human serum) and increased the ACE activity twofold to threefold. The Km and Vmax are reported for rat serum ACE (Hip-His-Leu) and dipeptidase (His-Leu) in borate buffer and phosphate buffer. Rat serum ACE hydrolysis of Hip-His-Leu measured by fluorometry correlated (r = 0.99, p less than 0.05) with the hydrolysis of angiotensin I measured by high-performance liquid chromatography. A direct method based on amino acid analysis is described for evaluating the dipeptidase error of complex mixtures such as tissue extracts and other physiological fluids. We have found that the assay can be used to measure ACE activity in 25 samples (in duplicate) in 2 hours with small intraassay (2.2%) and interassay (3.9%) coefficients of variation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:An improved fluorometric assay of rat serum and plasma converting enzyme. 298 18

The role of kinins in the hypertensive response to acute renal artery constriction (RAC) was examined in the dog. RAC resulted in an increase in systemic arterial pressure (SAP) from 144 +/- 6 to 155 +/- 4 mm HG (p less than 0.05). Simultaneously, arterial plasma bradykinin decreased from 2.3 +/- 0.2 to 1.4 +/- 0.1 ng/ml (p greater than 0.01), while renal venous bradykinin remained unchanged (2.3 +/- 0.2 to 2.0 +/- 0.4 ng/ml, p greater than 0.05). At the same time urinary kallikrein decreased from 55 +/- 6 to 33 +/- 4 milliesterase units (mEU)/min (p less than 0.05), while urinary kinin decreased from 3.2 +/- 0.4 to 1.9 +/- 0.3 ng/min (p less than 0.05). There was a significant correlation between the decrease in arterial bradykinin and the rise in SAP induced by RAC (p less than 0.01). Administration of the dipeptidyl hydrolase inhibitor SQ20881 during RAC reduced angiotensin-converting enzyme levels from 578 +/- 86 to 10 +/- 0.0 mU/ml (p less than 0.005). There was an associated increase in arterial bradykinin (1.4 +/- 0.1 to 5.8 +/- 0.8 ng/ml, p less than 0.001), renal venous bradykinin (2.0 +/- 0.4 to 5.7 +/- 0.5 ng/ml, p less than 0.005), and urinary kinin (1.9 +/- 0.3 to 5.0 +/- 0.7 ng/min, p less than 0.01) in conjunction with return of SAP to control levels. Urinary kallikrein, however, remained depressed following SQ20881 (33 +/- 4 to 30 +/- 5 mEU/min, p greater than 0.05). These results suggest that (1) decreases in circulating BK may potentiate the vasoconstrictor effect of angiotensin II and contribute to the hypertension induced by RAC, and (2) urinary kallikrein is an unreliable marker of changes in plasma bradykinin in this model of hypertension.
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PMID:Plasma kinin levels in acute renovascular hypertension in dogs. 620 Sep 3

In an attempt to clarify whether glomerular capillary pressure (Pgc) in hypertension can be reduced by a calcium channel blocker (CaB), renal clearance and micropuncture experiments were carried out on male heminephrectomized spontaneously hypertensive rats (SHR; n = 15). Renal circulatory parameters (RBF and GFR) and proximal tubular stop flow pressure (Psf) were measured during the control period, during manual aortic clamping, and after administration of manidipine hydrochloride (MDP, 10 micrograms/kg body weight in bolus). Because Psf only represents Pgc during zero tubular flow, the responsiveness of tubulo-glomerular feedback (TG feedback) was also assessed to obtain the "steady state Pgc", an operating point in each experimental period. Administration of MDP decreased systemic blood pressure (SBP) and renal vascular resistance (RVR), but increased renal blood flow (RBF) significantly. Psf decreased following the administration of MDP (33.65 +/- 1.45 mmHg), reaching a lower level than during aortic clamping (39.93 +/- 2.37 mmHg) or in the control period (50.78 +/- 2.73 mmHg). TG feedback responsiveness was attenuated during clamping, and was incompletely inhibited by MDP, whereas the operating point (29.3 mmHg) was lower than during clamping (32.9 mmHg) or in the control period (41.0 mmHg). The stability of RBF during the alteration of renal perfusion pressure (RPP) was not abolished by MDP. From these results, we suggest that MDP significantly decreases Pgc in the steady state not only by the reduction of RPP, but also by the amelioration of renal microcirculation.
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PMID:Effects of a calcium channel blocker, manidipine hydrochloride, on the regulatory mechanism of glomerular capillary pressure in SHR. 775 3

Monocrotaline (MONO), a pyrrolizidine alkaloid, causes veno-occlusive disease of the liver, pulmonary arterial hypertension, and right ventricular hypertrophy. Toxicity is due to the hepatic formation of a pyrolic metabolite that can be detoxified by conjugation with glutathione (GSH). We have shown that the GSH content of the liver affects the quantity of the pyrrolic metabolite that is released from the liver. We have now examined whether MONO, in turn, affects GSH metabolism. Twenty-four hours after administration of MONO to rats (65 mg/kg, i.p.), the highest concentration of bound pyrrolic metabolites was found in the liver, followed by the lung and kidney. Heart and brain contained lower concentrations of these metabolites. Significantly higher levels of GSH were found in liver and lungs of MONO-treated rats than in saline-injected control animals. In the liver, activities of the following enzymes were elevated: gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, dipeptidase, and microsomal GSH transferase. The same changes were seen in the lung. In the heart, gamma-glutamyl transpeptidase activity was decreased markedly, and cytosolic GSH transferase activity was elevated. In the kidney, the activities of GSH synthetase, gamma-glutamyl transpeptidase, and cytosolic GSH transferase were increased. Our results establish a mutual interaction of MONO and sulfur metabolism. It appears that an early metabolic action of MONO is to modify sulfur amino acid metabolism, diverting cysteine metabolism from oxidation to taurine towards synthesis of GSH.
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PMID:Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in the rat. 857 5

N-(7-Oxoacyl)-L-alanyl-D-isoglutamines are substances with similar effects on immune system as N-acetylmuramyldipeptide (MDP). They were synthesized to eliminate some side effects of MDP: pyrogenicity, leucopenia, hypertension and fast elimination from the body. The aim of our work was to determine some physicochemical properties of a series of N-(7-oxoacyl)-L-alanyl-D-isoglutamines, that have zero to six methylene groups between terminal methyl and 7-oxo group. The following properties were examined: water solubility, lipophilicity, thermal behaviour and true density. The results were compared and it was established that the lipophilic parameter determined by high-performance liquid chromatography is increasing by the increase of alkyl chain while the water solubility is decreasing at the same time. In both cases the substance with the longest chain (N-(7-tetrakanoyl)-L-alanyl-D-isoglutamine) is an exception. The lipophilic parameter of this substance is lower and water solubility higher than with the substances with three, four and five methylene groups between terminal methyl and 7-oxo group. These results can be explained by the twisted conformation of N-(7-tetrakanoyl)-L-alanyl-D-isoglutamine molecule in water solution. By means of thermal analysis it was discovered that the melting point is decreasing with the increase of alkyl chain. From the true density and melting enthalpy measurements it is evident that with the increase of alkyl chain the arrangement of molecules in solid state is increasing up to the molecule with four methylene groups between terminal methyl and 7-oxo group. Substances with longer chains have lower true density and melting enthalpy because of the different arrangements of the molecules.
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PMID:Some physicochemical properties of 7-oxoacyl-L-alanyl-D-isoglutamines. 1050 26

Angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor ocatapeptide angiotensin II, by removing two C-terminal amino acids. ACE is well known as a key part of the renin angiotenisn system that regulates blood pressure, and its inhibitors have potential for the treatment of hypertension. This paper reviewed the characteristics of ACE in aspects of its structure-function relationship, gene polymorphism and inhibitor development. In particular, the catalytic mechanisms of the two active sites of somatic ACE in the cleavage of angiotensin I and bradykin are different. Therefore, it would likely provide a new way for exploiting novel ACE inhibitors with fewer side-effects by specifically-targeting the individual active sites of somatic ACE.
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PMID:[Structure and function of angiotensin converting enzyme and its inhibitors]. 1846 95

The SHROB (spontaneously hypertensive rat - obese strain) is a model of prediabetes and metabolic syndrome with insulin resistance, glucose intolerance and hypertension. Inhibitors of dipeptidyl dipeptidase IV (DPP-IV) are effective hypoglycemic agents in type 2 diabetes through potentiation of incretin hormones that act in the pancreas to increase insulin and decrease glucagon release. We sought to determine whether the DPP-IV inhibitor sitagliptin might be effective in prediabetes relative to standard therapy with the sulfonylurea glyburide, by using the SHROB model. SHROB show normal fasting glucose but are insulin resistant and hyperglucagonemic. SHROB were treated for six weeks with vehicle, sitagliptin (30 mg/kg/d) or glyburide (1 mg/kg/d) and compared with untreated lean spontaneously hypertensive rats. Body weight, food intake and fasting glucose were all unchanged in all three SHROB groups, but glucagon was reduced by 33% by sitagliptin while remaining unchanged following glyburide or vehicle. In oral glucose (6 g/kg) tolerance testing, both sitagliptin and glyburide lowered plasma glucose. Both sitagliptin and glyburide shifted peak insulin secretion earlier (30 min for glyburide and 60 min for sitagliptin but 240 min for vehicle). Only sitagliptin significantly enhanced insulin secretion. Sitagliptin is effective in normalizing excess glucagon levels and delaying exaggerated insulin secretion in response to a glucose challenge in a prediabetic model.
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PMID:Sitagliptin lowers glucagon and improves glucose tolerance in prediabetic obese SHROB rats. 2134 31

Metabolic syndrome (MS), overlapping type 2 diabetes, hyperlipidemia, and/or hypertension, owing to high-fat diet, poses risk for cardiovascular disease. A critical feature associated with such risk is the functional impairment of endothelial progenitor cells (EPCs). Dipeptidyl dipeptidase-4 inhibitors (DPP-4 i) not only inhibit degradation of incretins to control blood glucose levels, but also improve EPC bioactivity and induce anti-inflammatory effects in tissues. In the present study, we investigated the effects of such an inhibitor, MK-06266, in an ischemia model of MS using diet-induced obese (DIO) mice. EPC bioactivity was examined in MK-0626-administered DIO mice and a non-treated control group, using an EPC colony-forming assay and bone marrow cKit+ Sca-1+ lineage-cells, and peripheral blood-mononuclear cells. Our results showed that, in vitro, the effect of MK-0626 treatment on EPC bioactivities and differentiation was superior compared to the control. Furthermore, microvascular density and pericyte-recruited arteriole number increased in MK-0626-administered mice, but not in the control group. Lineage profiling of isolated cells from ischemic tissues revealed that MK-0626 administration has an inhibitory effect on unproductive inflammation. This occurred via a decrease in the influx of total blood cells and pro-inflammatory cells such as neutrophils, total macrophages, M1, total T-cells, cytotoxic T-cells, and B-cells, with a concomitant increase in number of regeneration-associated cells, such as M2/M ratio and Treg/T-helper. Laser Doppler analysis revealed that at day 14 after ischemic injury, blood perfusion in hindlimb was greater in MK-0626-treated DIO mice, but not in control. In conclusion, the DPP-4 i had a positive effect on EPC differentiation in MS model of DIO mice. Following ischemic injury, DPP-4 i sharply reduced recruitment of pro-inflammatory cells into ischemic tissue and triggered regeneration and reparation, making it a promising therapeutic agent for MS treatment.
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PMID:Dipeptidyl dipeptidase-4 inhibitor recovered ischemia through an increase in vasculogenic endothelial progenitor cells and regeneration-associated cells in diet-induced obese mice. 3088 82


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