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)

The primary structure of human renin, recently established from the complementary DNA sequence of its messenger RNA, shows a strong homology to other aspartyl proteases. This homology has permitted the construction of a model of the three-dimensional structure of renin based on the crystallographically determined structures of three aspartyl proteases: penicillopepsin, endothiapepsin, and rhizopuspepsin. Using an algorithm in which a spherical probe approximating the size of the antibody-binding domain (1-nm radius) was allowed to contact the surface of the renin model, we predicted 12 to 15 peptides to be immunogenic epitopes. We synthesized peptides corresponding to three different regions of the model: Cys-Gly-Ser-Asp-Pro-Gln-His-Tyr-Glu-Gly-amide (C-180-188), Tyr-Leu-Leu-Cys-Glu-Asp-Gly-Cys-Leu-Ala-Leu-amide (Y-215-224; disulfide bond between cysteines) and Tyr-Gly-Ser-Ser-Thr-Leu-Leu-Cys-Glu-Asp-Gly-Cys-Leu-Ala-Leu-amide (Y-211-224; disulfide bond between cysteines), and Cys-Tyr-Ser-Ser-Lys-Lys-Leu-Cys-Gly (C-290-296-G; disulfide bond between cysteines). All four peptides were tested for their binding to 11 polyclonal and 7 monoclonal antibodies raised against pure human renin, in both a solution assay and an enzyme-linked immunosorbent assay. Peptides Y-215-224 and Y-211-224 bound to all 11 polyclonal antibodies in the solution assay, and peptide Y211-224 bound to eight of them in the enzyme-linked immunosorbent assay. Therefore, region 211-224 can be identified as a major epitope of the human renin molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Jun
PMID:Study of the antigenic determinants of human renin. 242 34

Rapid inhibition of urokinase in plasma obtained from women in the third trimester of pregnancy was assessed by the addition of 75 IU urokinase per ml plasma, and measurement of residual urokinase activity with PyroGlu-Gly-Arg-pNA after 5 minutes incubation at 37 degrees C. The urokinase inhibitory capacity was markedly increased for the pregnant women compared to non-pregnant controls. Alpha 1-antitrypsin, alpha 2-macroglobulin and alpha 2-antiplasmin did not account for the activity. Inhibition was higher for women with multiple gestations or macrosomia (n = 11) compared to normal pregnant women (n = 35) suggesting that the placenta contributes significantly to the measured activity. Inhibition was lower for women with hypertension (n = 33) compared to the normal pregnant women. Although the etiology for this difference is unclear, the decreased inhibitory activity may contribute to the increased risk for placental abruption that is observed for this group of women.
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PMID:The rapid inhibition of urokinase by plasma from pregnant women at risk for abruptio placenta. 243 78

Excretion patterns of kidney related urinary proteins such as lysosomal beta-N-acetylglucosaminidase (beta NAG), brush-border Ala-(Leu-Gly)-aminopeptidase (AAP), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (AP) as well as of IgG, albumin, and alpha-1-microglobulin, were assessed in patients with chronic glomerulonephritis (n = 53), pyelonephritis (n = 27), systemic lupus erythematodes (n = 5), and patients with essential arterial hypertension (n = 18). Excretion of tubular marker enzymes and serumproteins (related to urine creatinine concentration = protein creatinine index) in spontaneously voided second morning urine was significantly higher as compared to the controls (n = 2). Alpha-1-microglobulin was markedly elevated in both pyelonephritis and glomerulonephritis indicating disturbance in tubulointerstitial handling of microglobulins also in cases with primary glomerulopathy. Rise of albumin, IgG, and alpha-1-microglobulin as well as of tubular kidney markers AAP, AP, GGT, and beta NAG in cases with arterial hypertension without preexisting nephropathy support the hypothesis of a defect in charge and size permselectivity in these patients which is probably due to an increase in glomerular capillary perfusion pressure and hyperfiltration.
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PMID:Kidney- and serum derived proteins in urine of patients suffering from renal diseases or arterial hypertension. 247 9

Earlier studies from this laboratory had indicated that there is a selective increase in the density of brain kappa opioid receptors labeled with [3H]ethylketocyclazocine in spontaneously hypertensive (SHR) rats in comparison to normotensive Wistar-Kyoto rats. The binding of a mu-ligand, [3H]naltrexone, and a delta-ligand, [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr, to brain membranes of hypertensive and normotensive rats did not differ. The present studies were undertaken to determine further the role of kappa opioid receptors in hypertension. The binding of [3H]ethylketocyclazocine to brain membranes of hypertensive rats was much greater than those of normotensive rats. The density of kappa receptors was significantly higher in hypothalamic membranes of hypertensive rats as compared to normotensive rats. In order to determine the functional significance of the increased density of brain kappa opioid receptors in SHR rats, the effect of the kappa receptor agonists, tifluadom, U-50,488H and bremazocine, on two known actions associated with kappa receptors, namely analgesia and diuresis, were determined in SHR and normotensive rats. All three kappa agonists produced dose-dependent analgesia as measured by the tail-flick test. The intensity of the analgesic responses at each dose of the drugs in SHR rats was much greater than in normotensive Wistar-Kyoto rats. The kappa drugs also produced dose-dependent diuretic effects when the rats were loaded with 5% saline intragastrically. The increases in the volumes of urine produced by kappa drugs were much greater in SHR rats in comparison to normotensive rats. The basal tail-flick reaction time or urinary output in the two strains did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kappa opioid receptor activity in spontaneously hypertensive rats. 283 73

Tyrosine-MIF-1 (Tyr-Pro-Leu-Gly-NH2) is present in rat brain in varying concentrations throughout the day and can act as an opiate antagonist. Since altered sensitivity to pain is known to occur in hypertension, plasma and brain concentrations of Tyr-MIF-1--like immunoreactivity were measured in spontaneously hypertensive rats (SHR) and compared every 4 hours for 24 hours with the concentrations in control Wistar-Kyoto rats (WKY). The Tyr-MIF-1--like immunoreactivity in plasma was significantly higher in SHR than in the WKY at each interval; the mean difference was 62% (p less than 0.001). High-performance liquid chromatography demonstrated that peak immunoreactivity eluted in the same position as the synthetic tetrapeptide. Brain concentrations of the peptide were not reliably different between SHR and WKY. The diurnal rhythm was particularly evident in SHR: the highest concentrations of peptide in both brain and plasma occurred at 2000 hours. These results suggest the presence of another difference between SHR and WKY.
Hypertension 1986 Mar
PMID:Immunoreactive plasma concentrations of an endogenous antiopiate are higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. 286 91

The purpose of this study was to assess the role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor (CEI) enalaprilat in rats with severe hypertension induced by aortic ligation between both renal arteries. For this study, we used a bradykinin analogue, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA, with in vivo antagonistic properties. Hypertensive rats were infused intra-aortically for 15 minutes with either saline (30 microliters/min) or the kinin antagonist (40 micrograms/kg/min). Five minutes after the infusion was begun, a bolus injection of enalaprilat (60 micrograms/kg) was given. The blood pressure of the saline-infused animals decreased 48 +/- 6 mm Hg (from 180 +/- 7 to 132 +/- 7 mm Hg), while that of the rats treated with the antagonist decreased only 21 +/- 4 mm Hg (from 175 +/- 3 to 154 +/- 3 mm Hg). The difference between both decrements was significant (p less than 0.01). In another group of hypertensive animals (n = 9), we measured kinin concentration in plasma from arterial blood before and after administration of CEI (41 +/- 10 vs 68 +/- 20 pg/ml, respectively; NS). These results are consistent with the hypothesis that kinins play a role in the acute antihypertensive effect of CEIs in rats with severe hypertension. However, since arterial blood kinin concentrations were not increased significantly after CEI administration, the effect of the CEI may be due to an increase in tissue kinins, which could act as autacoids regulating vascular resistance.
Hypertension 1988 Mar
PMID:Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension. 289 70

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Jun
PMID:Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue. 289 59

The renal and hypotensive responses to intravenous infusions of 10, 50, 100, and 200 pmol/kg/min of synthetic rat atrial natriuretic factor (Arg101-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile110-Asp-Arg-Ile-G ly-Ala-Gln-Ser-Gly -Leu-Gly120-Cys-Asn-Ser-Phe-Arg-Tyr; disulfide bond between cysteines) were compared with those produced by synthetic human atrial natriuretic factor (Met110) in five conscious dogs. Increasing doses of rat or human atrial natriuretic factor lowered mean arterial pressure in a dose-related manner. At 200 pmol/kg/min, the maximally effective dose for both peptides, mean arterial pressure was reduced from 116 +/- 4 to 96 +/- 5 mm Hg and from 117 +/- 5 to 100 +/- 3 mm Hg (p less than 0.01), respectively. Neither peptide affected heart rate. Fractional sodium excretion increased from 0.69 +/- 0.22 to 3.95 +/- 1.23% and from 0.69 +/- 0.16 to 4.62 +/- 0.72% during infusions of 200 pmol/kg/min of rat and human atrial natriuretic factor, respectively. Urine volume and fractional chloride excretion rose during infusions of rat or human atrial natriuretic factor in a manner that resembled the elevation in sodium excretion. The stimulation of fractional potassium excretion by both rat and human peptides was more variable and not as clearly dose-dependent. Glomerular filtration rate was enhanced by both rat and human atrial natriuretic factor, while neither peptide significantly changed renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Mar
PMID:A comparison of synthetic rat and human atrial natriuretic factor in conscious dogs. 293 82

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.
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PMID:Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site. 297 76

Synthetic atrial natriuretic factor (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly -Leu- Gly-Cys-Asn-Ser-Phe-Arg-Tyr-COOH [disulfide bond between cysteines]) was infused intravenously into conscious normotensive and deoxycorticosterone, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats. Mean arterial pressure, urine volume, and electrolyte excretion rates were measured during a 20-minute infusion of a single dose (ranging from 0-1520 pmol/min) into each animal; 95 to 380 pmol/minute of synthetic atrial natriuretic factor maximally reduced mean arterial pressure by -20 +/- 4, -29 +/- 2, and -39 +/- 7 mm Hg in normotensive, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats, respectively. In deoxycorticosterone rats, a dose of 760 pmol/minute was required to produce the largest depressor response (-58 +/- 12 mm Hg). Sodium excretion increased to 8.8 +/- 2.5 muEq/minute at 760 pmol/minute in normotensive rats, to 6.5 +/- 1.1 muEq/minute at 50 pmol/minute in deoxycorticosterone rats, and to 5.8 +/- 1.5 muEq/minute at 95 pmol/minute in one-kidney, one-clip animals. The natriuretic effect was consistently greater at all doses of synthetic atrial natriuretic factor in the two-kidney, one-clip hypertensive model, in which the maximum response was 15.3 +/- 4.7 muEq/minute at 190 pmol/minute. The changes in urine volume and excretion rates of potassium and chloride tended to parallel the increases in sodium excretion in each model. Interestingly, the maximally effective hypotensive dose of synthetic atrial natriuretic factor was different from the maximally effective natriuretic dose in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Synthetic atrial natriuretic factor in conscious normotensive and hypertensive rats. 298 24


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