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

Recently, a parathyroid hypertensive factor was postulated to play a role in the pathogenesis of hypertension in genetically hypertensive rats. Therefore it was examined, whether in human parathyroid glands a vasopressor substance can be detected. For this purpose, homogenates of hyperplastic parathyroid glands from 20 patients with tertiary hyperparathyroidism were deproteinized and fractionated by gel chromatography. The fractions obtained were tested for vasopressor activity in isolated perfused rat kidneys. A vasopressor fraction containing substances of 0.6-2.5 kDa was identified in the parathyroid glands. The responsible product was heat sensitive, peptidase-, trypsin- and carboxypeptidase y- sensitive and hydrophilic, as it did not bind to hydrophobic reversed-phase gel. These results suggest that parathyroid glands contain a hydrophilic peptide-like vasopressor substance different from the parathyroid hormone.
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PMID:A vasopressor factor partially purified from human parathyroid glands. 141 52

Inhibitors of two zinc metallopeptidases, angiotensin I converting enzyme (ACE) and neutral metalloendopeptidase-24.11 (EP-24.11), are antihypertensive agents. In this issue of Hypertension, Genden and Molineaux report that yet another peptidase inhibitor, metalloendopeptidase-24.15, EC 3.4.24.15 (EP-24.15), lowers blood pressure in normotensive rats. In this editorial we discuss the possible role of kinins as common mediators of part of the vasodepressor action of these peptidase inhibitors. Genden and Molineaux report that the marked fall in blood pressure caused by the EP-24.15 inhibitor is almost abolished by a kinin receptor antagonist, supporting the hypothesis that kinins play a role in the regulation of normal blood pressure. We have confirmed that the EP-24.15 inhibitor used by these investigators lowers blood pressure. Up to now, EP-24.15 has not been implicated in in vivo metabolism of kinins. Although a number of kininases have been identified, our own previous work indicated that the metabolic pathway responsible for clearing kinins from the circulation involves the action of kininase II (angiotensin I converting enzyme) and renal peptidases. Nevertheless, the main metabolic pathway involved some other unidentified enzyme, since in these experiments disappearance of kinins from the circulation was only marginally reduced by a "cocktail" of inhibitors of ACE, EP-24.11, and carboxypeptidase N. It could be that EP-24.15 is involved in kinin metabolism. However, a number of questions need to be answered with regard to the mechanism by which the EP-24.15 inhibitor lowers blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Sep
PMID:Zinc metallopeptidase inhibitors. A novel antihypertensive treatment. 188 49

Arterial plasma kinins and mean arterial pressure were measured in intact and bilaterally nephrectomized rats infused with vehicle or bradykinin to study the role of 1) angiotensin converting enzyme (ACE) and other peptidases and 2) the kidney (a kininase-rich organ) in the metabolism of kinins in vivo. Before the infusion, rats were pretreated with vehicle, enalaprilat (an ACE inhibitor), or a cocktail of kininase inhibitors containing 1) enalaprilat, 2) DL-2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid (MGTA), a carboxypeptidase N inhibitor, 3) phosphoramidon, a neutral endopeptidase 24.11 inhibitor, and 4) bestatin, an aminopeptidase B inhibitor. In the rats with vehicle (n = 8), the cocktail did not significantly increase endogenous kinins (from 31 +/- 6 to 41 +/- 9 pg/ml, p = 0.94). In the rats infused with bradykinin (peptidase substrate), plasma kinins increased threefold in the group pretreated with the vehicle, 21-fold in the enalaprilat group, and 22-fold in the cocktail group. These increases were doubled by nephrectomy but were not affected by ureteral ligation. In the groups pretreated with the cocktail or enalaprilat, the hypotensive effect of bradykinin was correlated with plasma kinin concentration (r = 0.75, p less than 0.001). After bradykinin infusion was stopped, plasma kinins decreased by half in 10-12 seconds in the rats pretreated with vehicle, enalaprilat, or cocktail. We concluded that ACE and the kidney are important to the metabolism of circulating kinins while carboxypeptidase N, neutral endopeptidase 24.11 and aminopeptidase B are not. We also concluded that other tissue peptidases, not affected by either the above inhibitors or nephrectomy, play an important role in kinin metabolism.
Hypertension 1989 Sep
PMID:Role of angiotensin converting enzyme and other peptidases in in vivo metabolism of kinins. 254 61

Angiotensin-converting enzyme is a peptidase involved in the formation of angiotensin II and the inactivation of bradykinin. In a previous study we found elevated angiotensin-converting enzyme activity in women with pregnancy-induced hypertension prior to magnesium sulfate therapy and lower levels during therapy. This prospective study was undertaken in order to determine if angiotensin-converting enzyme activity indeed decreased after magnesium sulfate therapy. Sixteen patients with pregnancy-induced hypertension were studied before and during magnesium sulfate therapy. Angiotensin-converting enzyme activity was found to decrease 1 to 8 hours into therapy and then plateau between 9 and 24 hours. Possible mechanisms for this observation are discussed.
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PMID:Angiotensin-converting enzyme activity in hypertensive subjects after magnesium sulfate therapy. 303 26

Angiotensin-converting enzyme, the peptidase hydrolysing angiotensin I to angiotensin II and first discovered in plasma, has been demonstrated in lung tissue on the luminal surface of endothelial cells lining pulmonary blood vessels. Because converting enzyme is the final activating step in the renin-angiotensin system its inhibition prevents the pressor and other effects of increased renin secretion. Lung converting enzyme activity is inhibited specifically by a nonapeptide (BPP9a:SQ 20 881) contained in Bothrops jararaca venom. This peptide inhibits the pressor effects of injected angiotensin I in humans and lowers blood pressure in patients with high-renin hypertension. Recently a synthetic inhibitor, captopril, was devised which is effective, given orally, in reducing the blood pressure of high-renin hypertensives and of a proportion of hypertensives with normal renin levels. The latter finding suggests that blood pressure may be maintained by renin-dependent mechanisms without increased renin secretion.
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PMID:Pulmonary angiotensin-converting enzyme and its inhibition: a historical survey. 625 81

The effects of injection of a peptidase-resistant analog of methionine-enkephalin, [D-ala2]-methionine-enkephalin, on blood pressure (BP), heart rate, and vasopressin release were studied in spontaneously hypertensive rats (SHR). Intravenous injection of [D-Ala2]-methionine-enkephalin (DAME) increased BP in both SHR and normotensive Wistar-Kyoto (WKY) controls, with a significantly greater increase in hypertensive rats. Intracerebroventricular injection of DAME produced a biphasic increase in BP and an increase in heart rate in both groups. The initial pressor effect was significantly greater in the SHR, Plasma vasopressin levels in SHR were depressed relative to both untreated hypertensive rats and animals given vehicle control injections. Intravenous pretreatment with a vasopressin vasopressor antagonist, [l-(beta-mercapto-beta-beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine] arginine-vasopressin, did not block either component of the central enkephalin response in hypertensive rats. These date indicate that central enkephalin injection does not release vasopressin and that SHR are hyperresponsive to enkephalin. It is concluded that pressor systems other than that of vasopressin mediate the enkephalin-induced cardiovascular effects.
Hypertension
PMID:Vasopressin release does not contribute to pressor action of enkephalin in SHR. 730 4

We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis from eight rats. The different samples were homogenized and centrifuged (2000g during 20 minutes), and the supernatant was incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the presence of peptidase inhibitors. Kinins released were measured by radioimmunoassay. Kininogenase activity was found in rat uteri, placental vessels, amniotic fluids, and fetal membranes. The enzymes were present in active but mostly in inactive forms. The kallikrein-like enzymes found in the different preparations and rat urinary kallikrein used as control had similar molecular weights, immunologic characteristics, and inhibition profiles with protease inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of reproduction. These data suggest that kinins released locally may act as paracrine hormones in the regulation of blood pressure during pregnancy.
Hypertension 1994 Jan
PMID:Biochemical evidence of a kallikrein-like activity in rat reproductive tissues. 828 57

Acute hypertension provokes a rapid decrease in proximal tubule sodium reabsorption with a decrease in basolateral membrane sodium-potassium-ATPase activity and an increase in the density of membranes containing apical membrane sodium/hydrogen exchangers (NHE3) [Y. Zhang, A. K. Mircheff, C. B. Hensley, C. E. Magyar, D. G. Warnock, R. Chambrey, K.-P. Yip, D. J. Marsh, N.-H. Holstein-Rathlou, and A. A. McDonough. Am. J. Physiol. 270 (Renal Fluid Electrolyte Physiol. 39): F1004-F1014, 1996]. To determine the reversibility and specificity of these responses, rats were subjected to 1) elevation of blood pressure (BP) of 50 mmHg for 5 min, 2) restoration of normotension after the first protocol, or 3) sham operation. Systolic hypertension increased urine output and endogenous lithium clearance three- to fivefold within 5 min, but these returned to basal levels only 15 min after BP was restored. Renal cortex lysate was fractionated on sorbitol gradients. Basolateral membrane sodium-potassium-ATPase activity (but not subunit immunoreactivity) decreased one-third to one-half after BP was elevated and recovered after BP was normalized. After BP was elevated, 55% of the apical NHE3 immunoreactivity, smaller fractions of sodium-phosphate cotransporter immunoreactivity, and apical alkaline phosphatase and dipeptidyl-peptidase redistributed to membranes of higher density enriched in markers of the intermicrovillar cleft (megalin) and endosomes (Rab 4 and Rab 5), whereas density distributions of the apical cytoskeleton protein villin were unaltered. After 20 min of normalized BP, all the NHE3 and smaller fractions of the other apical membrane proteins returned to their original distributions. These findings suggest that the dynamic regulation of proximal tubule sodium transport by acute changes in BP may be mediated by rapid reversible regulation of sodium pump activity and relocation of apical sodium transporters.
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PMID:Reversible effects of acute hypertension on proximal tubule sodium transporters. 957 7

Endogenous peptidases participate in a major way in the formation of peptide pressor substances such as angiotensin II (A II) and endothelin (ET) as well as in the degradation of depressor substances, e.g. atrial natriuretic peptide (ANP) or bradykinin. They include on the one hand the angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE), on the other hand kinase II for bradykinin and neutral endopeptidase 24.11 (NEP) for ANP. Inhibition of these enzymatic reactions leads to a decline of vasopressors A II and ET and conversely delays the break-down of vasodilatating bradykinin and ANP. The main haemodynamic consequence of this double inhibition is a reduced peripheral vascular resistance and decline of the blood pressure. The concurrent block of both systems (dual inhibition) is more effective than the isolated block of one substance. The first dual endopeptidase inhibitors were ACE inhibitors blocking the conversion of angiotensin I to A II and inhibiting at the same time the degradation of bradykinin by kininase II which is identical with ACE. At present further substances were synthetized with a dual inhibitory effect e.g. on ECE and on NEP (phosphoramidone, thiorphan, ecadatril etc.). Under experimental conditions they have a long-term antihypertensive effect on the vascular wall and heart muscle. The development of another dual ACE and NEP inhibitor has reached already the stage of clinical tests and the first clinical studies. The preparation omapatrilate in amounts of 2.5-80 mg significantly reduced the BP in a dose-dependent way in mild and medium advanced essential hypertension. Normalization of the blood pressure, i.e. a drop below 140/90 mm Hg, was achieved with omapatrilate monotherapy in as many as 83% of patients with hypertension stage I and in 53% patients with essential hypertension stage II. The drop of blood pressure after 20-80 mg/day depended on the degree of hypertension and was comparable or better than monotherapy with lisonopril 20 mg/day or amlodipine 10 mg/day. Treatment with omapatrilate was well tolerated. Dual peptidase inhibitors interfering with the formation of pressor substances and with the degradation of depressor substances seem to be a perspective class of antihypertensives also useful in the treatment of other cardiovascular diseases (heart failure, primary pulmonary hypertension). Before its final inclusion in the therapeutic pattern, further comparative and clinical mortality studies must be implemented.
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PMID:[Dual endopeptidase inhibitors--a new direction in the development of hypertensive agents]. 1104 16

Human heart tissue enzymes cleave angiotensin (Ang) I to release Ang 1-9, Ang II, or Ang 1-7. In atrial homogenate preparations, cathepsin A (deamidase) is responsible for 65% of the liberated Ang 1-9. Ang 1-7 was released (88% to 100%) by a metallopeptidase, as established with peptidase inhibitors. Ang II was liberated to about equal degrees by ACE and chymase-type enzymes. Cathepsin A's presence in heart tissue was also proven because it deamidated enkephalinamide substrate by immunoprecipitation of cathepsin A with antiserum to human recombinant enzyme and by immunohistochemistry. In immunohistochemistry, cathepsin A was detected in myocytes of atrial tissue. The products of Ang I cleavage, Ang 1-9 and Ang 1-7, potentiated the effect of an ACE-resistant bradykinin analog and enhanced kinin effect on the B(2) receptor in Chinese hamster ovary cells transfected to express human ACE and B(2) (CHO/AB), and in human pulmonary arterial endothelial cells. Ang 1-9 and 1-7 augmented arachidonic acid and nitric oxide (NO) release by kinin. Direct assay of NO liberation by bradykinin from endothelial cells was potentiated at 10 nmol/L concentration, 2.4-fold (Ang 1-9) and 2.1-fold (Ang 1-7); in higher concentrations, Ang 1-9 was significantly more active than Ang 1-7. Both peptides had traces of activity in the absence of bradykinin. Ang 1-9 and Ang 1-7 potentiated bradykinin action on the B(2) receptor by raising arachidonic acid and NO release at much lower concentrations than their 50% inhibition concentrations (IC(50)s) with ACE. They probably induce conformational changes in the ACE/B(2) receptor complex via interaction with ACE.
Hypertension 2002 May
PMID:Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A. 1201 79


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