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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has recently been claimed that there are angiotensin II (ANG II) receptors on human mononuclear cells and on platelets and this has been used for investigating the regulation of the renin-angiotensin system in hypertension. We here show the following. Binding kinetics of 125I-labelled ANG II and [3H]ANG II to mononuclear cells were slow (maximum at 90 min) and the same as for [3H]-inulin. As with [3H]inulin there was no binding at 4 degrees C. Release from the cells was slow and incomplete (about 30% after 15 min, 60% after 60 min). Binding was not saturable over a range from 10(-12) to 10(-6) mol of ANG II/l, about 8% of offered peptide being bound at all concentrations. Various inhibitors of free fluid endocytosis exhibited the same inhibition pattern of ANG II binding to mononuclear cells. Therefore uptake of ANG II into mononuclear cells displayed all the features of free fluid endocytosis. ANG II was degraded by carboxypeptidase A. When this degradation was prevented by D-phenylalanine, no binding occurred. In platelet preparations contaminated by 0.3-5% of mononuclear cells, 125I-labelled ANG II was degraded as well. Free fluid endocytosis of the degradation product strongly depended on the percentage of contaminating mononuclear cells. We conclude that there are no ANG II receptors on human mononuclear cells and that their presence on human platelets is doubtful.
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PMID:Angiotensin II binding to human mononuclear cells: receptor or free fluid endocytosis? 632 93

Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.
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PMID:Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. 1254 Aug 54

Lysosomal carboxypeptidases play important roles in catabolism of proteins and peptides and in posttranslational processing of other lysosomal enzymes. The major lysosomal serine carboxypeptidase A (cathepsin A [CathA]), also known as protective protein, activates and stabilizes two other lysosomal enzymes, beta-galactosidase and neuraminidase/sialidase 1. Genetic deficiency of CathA (galactosialidosis) causes the lysosomal storage of sialylated glycoconjugates and leads to a multiorgan pathology. The galactosialidosis patients also show arterial hypertension and cardiomyopathy, conditions not predicted from the lysosomal storage of glycoconjugates. This review summarizes the experimental data suggesting that both cardiovascular pathologies associate with persisted vasoconstrictions and impaired formation of the elastic fibers triggered by the deficiency of CathA. We also discuss the homologous serine carboxypeptidases, Scpep1 and vitellogenic-like carboxypeptidase, that are secreted from endothelial cells and could potentially affect the cardiovascular system.
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PMID:Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis. 1946 48

The angiotensin-converting enzyme (ACE) exhibits critical functions in the conversion of angiotensin I to angiotensin II and the degradation of bradykinin and other vasoactive peptides. As a result, the ACE inhibition has become a promising approach in the treatment of hypertension, heart failure, and diabetic nephropathy. Extending our recent molecular dynamics simulation of the testis ACE in complex with a bona fide substrate molecule, hippuryl-histidyl-leucine, we presented here a detailed investigation of the hydrolytic process and possible influences of the chloride ion on the reaction using a combined quantum mechanical and molecule mechanical method. Similar to carboxypeptidase A and thermolysin, the promoted water mechanism is established for the catalysis of ACE. The E384 residue was found to have the dual function of a general base for activating the water nucleophile and a general acid for facilitating the cleavage of amide C-N bond. Consistent with experimental observations, the chloride ion at the second binding position is found to accelerate the reaction rate presumably due to the long-range electrostatic interactions but has little influence on the overall substrate binding characteristics.
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PMID:Catalytic mechanism of angiotensin-converting enzyme and effects of the chloride ion. 2367 66