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)

1 In spontaneously hypertensive rat (SHR) we examined over a 4-week period the influence of control low sodium diet, common salt-enriched diet (sodium chloride 6% of the dry weight of the chow) and a novel mineral salt-enriched diet (potassium-, magnesium-, and l-lysine-enriched mineral salt added at a 75% higher level of 10.5% to produce the same sodium chloride concentration of 6%) on the cardiovascular effects produced by a low-dose combination of an angiotensin converting enzyme inhibitor ramipril (0.25 mg kg(-1) day(-1) in the food) and a calcium channel blocker felodipine (0.4 mg kg(-1) day(-1) subcutaneously via an osmotic minipump). 2 Common salt, but not the mineral salt, accelerated the development of hypertension and induced left ventricular and renal hypertrophy in SHR. Neither common salt nor mineral salt significantly affected heart rate. 3 The combination of ramipril and felodipine decreased systolic blood pressure and prevented the development of left ventricular hypertrophy effectively during the common salt diet without any significant effect on the heart rate. The cardiovascular effects of the drug combination were improved by the low sodium diet or by replacement of high common salt in the diet by mineral salt. 4 Responses of endothelium-intact mesenteric arterial rings in vitro were examined at the end of the four-week study. The combination of ramipril and felodipine markedly improved the endothelium-dependent vascular relaxation responses to acetylcholine and enhanced the endothelium-independent vascular relaxation responses to sodium nitroprusside in SHR on control and common salt diets. Replacement of common salt in the diet by mineral salt improved the endothelium-dependent vascular relaxation responses to acetylcholine. The drug combination attenuated the alpha-adrenoceptor-mediated vascular contractile responses to noradrenaline during the common salt diet. 5 Ramipril and felodipine in combination increased plasma renin activity by 1.9-3.2 fold without affecting serum aldosterone levels. 6 Our findings suggest that the cardiovascular effect of the low-dose combination of ramipril and felodipine was maintained during high salt intake. However, salt restriction or replacement of common salt in the diet by the potassium- and magnesium-enriched mineral salt improved the cardiovascular effects of the drug combination. In the face of a high intake of sodium, a part of the beneficial cardiovascular effects of the drug combination is apparently mediated by improved endothelium-dependent and endothelium-independent vascular relaxation responses and attenuated alpha-adrenoceptor-mediated vascular contractile responses.
 ...
PMID:Influence of dietary salts on the cardiovascular effects of low-dose combination of ramipril and felodipine in spontaneously hypertensive rats. 948 6

Taste preferences are altered to reflect physiological needs and to support the recovery from nutritional disorders. The central mechanism both recognition for and adaptation to a deficient essential nutrient, i.e. L-lysine, have been unveiled that the feeding center in the hypothalamus is a primary center nucleus to induce a neuronal plasticity responding to dietary intake of deficient nutrient in the brain and peripherally, such as sense of taste and its concentration change. Changing preferences may act as an alarm, signaling protein malnutrition or metabolic adult disease, such as hypertension for saltiness, diabetes for sweetness, etc. In addition, our consumption of alcohol beverage is still increasing despite of one of candidate to induce the hepatic disorders, because pharmacological function of alcohol in the brain is welcome for people enjoying meal or being relieved from stresses. Preference for both L-alanine and L-glutamine was observed when alcoholic rats fell in the hepatic disorder. Acute alcohol loading induced suppression of motor activity and the hepatic dysfunction, but both amino acids did obviously protect these alcoholic symptoms. People should have to require a little bit more specific L-amino acid physiologically and pharmacologically depending upon different states among aging, lifestyle, metabolic diseases and various stresses.
 ...
PMID:[A new pharmacological and physiological aspects of L-amino acids]. 950 1

The decision to use any pharmacologic intervention inevitably rests on balancing the efficacy and safety of the intervention. The advent of the acquired immunodeficiency syndrome epidemic greatly increased awareness of transfusion-related illnesses and focused attention on methods to prevent the need for blood and blood products. This has led, especially in the last decade, to increased use of drugs to help reduce perioperative bleeding. This chapter focuses on the lysine analogues and aprotinin as the serine protease inhibitor currently available in clinical practice. Both groups of compounds have recently shown promise in reducing surgical bleeding. However, the reader will notice that none of these agents are new; they have all been available for more than 30 years. What is new is their use in preventing bleeding. We therefore have considerable knowledge regarding the safety of these compounds. The first part of this review will compare the actions of these two types of agents on the processes related to thrombosis, hemostasis, and fibrinolysis. This is followed by a comparison of the efficacy of each intervention and any dose-response relationship. This section highlights the reported reduction in postoperative bleeding with both classes of agent. There is, however, no obvious or consistent reduction in the transfusion of blood and blood products in patients given lysine analogues. In contrast, there is a consistent reduction in the need for blood transfusions in patients given aprotinin therapy. The next major section will discuss the evidence to suggest that these drugs may, because of their known effects on the processes related to inflammation, hemostasis, and cellular repair, contribute to an improvement or worsening of outcome after cardiac operations. In particular, this section focuses on the antiinflammatory actions and modifications in vascular tone associated with aprotinin therapy. These effects may be related to improved outcome in patients by reducing the incidence of permanent neurologic deficit or stroke after heart operations, as well as inhibiting pulmonary vascular hyperreactivity and hypertension in susceptible individuals. Finally, this brief review discusses the safety issues that have been raised in regard to each of these classes of agents, specifically problems associated with abnormal renal function, hypersensitivity reactions, and thrombotic complications.
 ...
PMID:Aprotinin versus lysine analogues: the debate continues. 956 97

The functional protein that binds to human hemoglobin (hemoglobin-binding protein; HBP) was purified from Porphyromonas gingivalis cells. The analyses of the amino-terminal sequence and amino acid composition revealed that HBP is identical to lysine-specific cysteine proteinase (51 kDa Lys-gingipain; KGP) of P. gingivalis 381. It is a novel finding that KGP has binding affinity to hemoglobin. The binding activity of HBP was enhanced by acidic or anaerobic conditions. Arg-gingipain, a member of the gingipain family, of P. gingivalis exhibited no ability to bind to hemoglobin. The recombinant protein of KGP (r-KGP) generated in Escherichia coli showed both hemoglobin-binding and proteolytic activities. The treatment of r-KGP by protein disulfide isomerase effectively enhanced binding to hemoglobin, whereas the proteinase activity was decreased. The treated r-KGP significantly inhibited the binding of hemoglobin to the whole cell extracts in a dose-dependent manner. These results suggest that the hemoglobin binding of P. gingivalis is mediated by KGP through active domain(s) distinct from that for proteinase activity.
 ...
PMID:Hemoglobin-binding protein purified from Porphyromonas gingivalis is identical to lysine-specific cysteine proteinase (Lys-gingipain). 970 27

The influence of isosorbide-5-mononitrate (IS-5-MN) on the cardiovascular effects of high dietary salt intake (NaCl, 6.6% of dry weight of food) and that of a potassium, magnesium and l-lysine-enriched salt alternative (Pansalt 10.5%, producing a 6.6% content of NaCl) was studied in spontaneously hypertensive rats in an 8-week experiment. Common salt produced a marked rise in blood pressure and induced cardiac and renal hypertrophy, while the salt alternative, although containing the same amount of NaCl, neither increased blood pressure nor caused any significant cardiac hypertrophy. IS-5-MN treatment at a daily dose of approximately 60-70 mg/kg (mixed with food) attenuated the rise in blood pressure induced by common salt, but did not prevent the cardiac or renal hypertrophy. IS-5-MN did not offer any additional benefit to the use of the salt alternative diet alone in treatment of high blood pressure. Mesenteric arterial responses in vitro were examined at the end of the study. IS-5-MN treatment during the moderately low-salt (NaCl 0.7%) control diet tended to decrease the contractile response to noradrenaline and increase the relaxation to acetylcholine. Common salt, but not the salt alternative, induced a 50% increase in the 24-h urinary excretion of cyclic GMP. Both salt supplements induced an 8-9-fold increase in the excretion of calcium, and about a 2-fold increase in the excretion of phosphorus. Common salt also increased the excretion of magnesium by 50%. IS-5-MN treatment had no significant effect on the excretion of the mineral elements. Our findings show that increased intake of potassium and magnesium reduces the harmful effects of common salt. Pressure-independent mechanisms are involved in salt-induced left ventricular and renal hypertrophy, since they remained unaffected despite the prevention of the salt-induced rise in blood pressure by IS-5-MN treatment.
 ...
PMID:Cardiovascular effects of dietary salts and isosorbide-5-mononitrate in spontaneously hypertensive rats. 975 89

Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.
 ...
PMID:A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment. 1020 95

Lysine is one of the indispensible amino acids and L-lysine monohydrochloride (LMH) is widely available to public as a nonprescription oral supplement. Potential clinical usefulness of oral LMH supplements has been indicated in stroke, hypertension, and seizure induced by pentylenetetrazole (PTZ), etc. We compared the effects of LMH and flunarizine on the Electrocorticogram (EcoG) of rats intragastrically administered 1 hour before anoxia. LMH dose-dependently prolonged the time reaching the lowest ECoG average amplitude after anoxia and decreased the recovery time after recirculation in both 0.63 g/kg and 1.26 g/kg groups. There was significant difference between the LMH- and saline-pretreated groups but no significant difference between the 1.26 g/kg LMH- and 2.5 mg/kg flunarizine-pretreated groups. The difference was not significant in the 2.52 g/kg group. The ECoG average amplitude did not reach isoelectric point and the lowest average amplitude was 10 percent of that of nomoxia in the 1.26 g/kg LMH-pretreated group during 2-min anoxia. The average amplitude pretreated with LMH (0.63 and 1.26 g/kg) was lower than that of those pretreated with saline and flunarizine. The results tend to indicate that LMH can protect brain cells against anoxia by means of providing energy, reducing cerebral metabolic rate and inhibiting the effect of the excitable amino acids.
 ...
PMID:Neuroprotective effect of L-lysine monohydrochloride on acute iterative anoxia in rats with quantitative analysis of electrocorticogram. 1041 29

Steroid dehydrogenase enzymes influence mammalian reproduction, hypertension, neoplasia, and digestion. The three-dimensional structures of steroid dehydrogenase enzymes reveal the position of the catalytic triad, a possible mechanism of keto-hydroxyl interconversion, a molecular mechanism of inhibition, and the basis for selectivity. Glycyrrhizic acid, the active ingredient in licorice, and its metabolite carbenoxolone are potent inhibitors of human 11 beta-hydroxysteroid dehydrogenase and bacterial 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD). The three-dimensional structure of the 3 alpha, 20 beta-HSD carbenoxolone complex unequivocally verifies the postulated active site of the enzyme, shows that inhibition is a result of direct competition with the substrate for binding, and provides a plausible model for the mechanism of inhibition of 11 beta-hydroxysteroid dehydrogenase by carbenoxolone. The structure of the ternary complex of human 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD) with the cofactor NADP+ and the antiestrogen equilin reveals the details of binding of an inhibitor in the active site of the enzyme and the possible roles of various amino acids in the catalytic cleft. The short-chain dehydrogenase reductase (SDR) family includes these steroid dehydrogenase enzymes and more than 60 other proteins from human, mammalian, insect, and bacterial sources. Most members of the family contain the tyrosine and lysine of the catalytic triad in a YxxxK sequence. X-ray crystal structures of 13 members of the family have been completed. When the alpha-carbon backbone of the cofactor binding domains of the structures are superimposed, the conserved residues are at the core of the structure and in the cofactor binding domain, but not in the substrate binding pocket.
 ...
PMID:Steroid dehydrogenase structures, mechanism of action, and disease. 1066 97

The response of the kidney tissues to steroids, mainly dehydroepiandrosterone (DHEA), testosterone (T) and dihydrotestosterone (DHT) has been used extensively to investigate the mechanisms of steroid action on hypertension. The specific objective of this study was to investigate anatomical characteristics of kidney tissue after sustained delivery of DHEA, DHT or T at physiological or supraphysiological doses using adult male rats as a model. A total of eighteen adult male Sprague Dawley rats were divided randomly into six equal groups. Animals in groups I-V were implanted intraperitoneally with a single tricalcium phosphate lysine delivery system (TCPL) loaded with T (physiological dose), T (supraphysiological dose), DHT (physiological dose), DHT (supraphysiological dose), and DHEA (physiological dose), respectively. Animals in Group VI were implanted with empty TCPL capsules and served as sham controls. At the end of 21 days post implantation, the animals in each group were sacrificed and the kidneys were harvested, processed, embedded, sectioned and screened for cellular alterations. Data obtained from this study have shown physiological doses DHEA or supraphysiological doses of DHT and T had a significant effect on the areas of the glomeruli, without disruption or changes in area of proximal tubules. Histological evaluation of the organs (5 microns, H&E) revealed nephrotic hypotrophy in all kidneys obtained from animals given supraphysiological doses of DHT or T in comparison to sham animals.
 ...
PMID:Morphological investigation of the rat kidney after continuous administration of testosterone, dihydrotestosterone, or dehydroepiandrosterone using TCPL delivery devices. 1083 59

The vasopeptidase inhibitor omapatrilat inhibits both neutral endopeptidase and angiotensin-converting enzyme (ACE). The in vitro and in vivo inhibitory potency of omapatrilat and the specific ACE inhibitor fosinopril toward the 2 active sites of ACE (called N- and C-domains) was investigated with the use of 3 substrates: angiotensin I, which is equally cleaved by the 2 ACE domains; hippuryl-histidyl-leucine, specific synthetic substrate of the C-domain in high- salt conditions; and a newly synthesized specific substrate of the N-domain designed by acetylating the lysine residue of AcSDKP. In vitro, omapatrilat was 5 times more potent than fosinoprilat in inhibiting angiotensin I hydrolysis. Omapatrilat inhibited similarly both N- and C-domain hydrolysis, whereas fosinoprilat was slightly more specific for the N-domain. The in vivo selective inhibitory potency of single oral doses of 10 mg omapatrilat and 20 mg fosinopril were investigated in a double-blind, placebo-controlled, cross-over study in 9 mildly sodium-depleted normotensive subjects. In accordance with the in vitro results, fosinopril appeared to be more specific for the N-domain than the C-domain in vivo, since plasma and urine AcSDKP concentrations were significantly higher than those observed with omapatrilat. This study shows that it is possible to assess separately in vitro and in vivo the selectivity of ACE or ACE/neutral endopeptidase inhibitors. A differential selectivity may explain some peculiar properties observed with some ACE inhibitors.
Hypertension 2000 Jun
PMID:In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor. 1085 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>