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)

Myocardial taurine concentrations have been found to be elevated in hypertension and congestive heart failure states in animals and humans. The mechanism(s) by which myocardial taurine levels increase isn't known. Biosynthesis of taurine by the heart has not been established as a significant process. The fetal mouse heart in culture was used to characterize a taurine uptake system. The uptake of taurine was found to be saturable, temperature and sodium dependent and inhibited by close structural analogs. Taurine uptake was energy dependent and accumulated taurine against a concentration gradient indicating that taurine transport is an active process. Failure of alpha-alanine, alpha-aminoisobutyric acid, glycine, leucine or threonine to decrease taurine uptake establishes that the taurine uptake system is separate and distinct from other neutral alpha-amino acid transport systems in the heart.
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PMID:Carrier-mediated taurine uptake in the fetal mouse heart. 56 51

This study confirmed again that high protein diet feeding decreased the incidence of stroke, and high fish protein diet did attenuate severe hypertension but high soybean protein diet did not affect the hypertension. Dietary amino acid analyses indicated that increases in total amino acids, essential amino acids and nonpolar amino acids but not acid or basic amino acids were significantly related to the reduction of stroke incidence. Among essential amino acids, lysine, threonine, isoleucine, and leucine contents were inversely related to stroke incidence, and methionine content was significantly related to the dietary antihypertensive effect of high protein diets. The prophylactic effect of high protein diets may be ascribed to some amino acid constituent.
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PMID:Prophylactic trials for stroke in stroke-prone SHR. (3) Amino acid analysis of various diets and their prophylactic effect. 56 25

Cardiac taurine levels are elevated in hypertension and congestive heart failure. A possible mechanism for this increase in taurine is an alteration of its uptake. We sought to identify and characterize a carrier-mediated transport system for taurine in the mammalian myocardium utilizing the fetal mouse heart in organ culture. Hearts from fetuses of 16-19 days gestational age used in these studies had an endogenous taurine content of 14.1+/-0.5 nmol/mg tissue. The uptake of [(3)H]taurine was linear for up to 8 h. Taurine was accumulated against a concentration gradient as demonstrated by a net increase in taurine concentration when hearts were incubated in 0.5 mM taurine. [(3)H]Taurine uptake was saturable, K(m) = 0.44 mM, temperature dependent, and required sodium. The close structural analogues, hypotaurine and beta-alanine, reduced [(3)H]taurine uptake by 87% when present in 100-fold excess. The alpha-amino acids alanine, alpha-aminoisobutyric acid, glycine, leucine, and threonine did not inhibit uptake. Other taurine analogues tested were guanidinotaurine, guanidinopropionic acid, gamma-aminobutyric acid, 2-aminoethane phosphonic acid, aminomethane sulfonic acid, 3-aminopropane sulfonic acid, N-acetyltaurine, and isethionic acid. We conclude that a carrier-mediated transport system for taurine exists in the fetal mouse heart based on the demonstration of (a) temperature dependence, (b) saturability, and (c) structural selectivity of the uptake process. Transport was demonstrated to be mediated by a beta-amino acid uptake system. In addition, taurine uptake was observed to be sodium dependent, energy dependent, and capable of accumulating taurine against a concentration gradient.
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PMID:Characterization of a carrier-mediated transport system for taurine in the fetal mouse heart in vitro. 65 83

The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.
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PMID:Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. 128 Mar 21

This study was undertaken in order to investigate the newly discovered spontaneously hypertensive rat (SHR)-specific restriction fragment length polymorphism (RFLP) at the genomic locus of (poly)phosphoinositide-specific phospholipase C (PLC)-delta at a DNA sequence level. Our aim was to clone the PLC-delta complimentary DNA (cDNA) from SHR and analyse the genomic DNA obtained from two hypertensive rat strains such as SHR and its stroke-prone substrain (SHR-SP) and three normotensive rat strains such as Sprague-Dawley, Donryu and Wistar-Kyoto (WKY) by preparing an aortic cDNA library of SHR, hybridization cloning of PLC-delta cDNA and an analysis of the genomic DNA by polymerase chain reaction. By digesting with restriction enzyme XhoI, we discovered an RFLP band displaying only in SHR and SHR-SP, not in Sprague-Dawley, Donryu and WKY rats. DNA sequencing of PLC-delta cDNA cloned from an aortic cDNA library of SHR revealed a total of three SHR-specific point mutations, two of which resulted in amino acid substitutions. The first point mutation (A to T) was detected at the XhoI site, changing a threonine(ACG) to a serine(TCG), and the second point mutation (A to G) was discovered in the vicinity of the first one, changing an isoleucine(ATA) to a methionine(ATG). This is the first demonstration of the mutations in the SHR genome changing amino acid sequences. These amino acid substitutions, situated in the putative catalytic X domain of PLC-delta, may be the major cause of the augmented PLC activity observed in the SHR, possibly leading to hypertension-related phenonemoma such as abnormal calcium homeostasis and increased intracellular calcium ion concentrations.
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PMID:Phospholipase C-delta gene of the spontaneously hypertensive rat harbors point mutations causing amino acid substitutions in a catalytic domain. 168 14

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

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

We investigate the effect of a new angiotensin-converting enzyme inhibitor: Perindopril (IRIS) on regression of left ventricular hypertrophy (LVH), coronary blood flow and mechanical performance of isolated papillary muscle in renovascular hypertensive (Goldblatt 2 kidneys-1 clip) Sprague-Dawley male rats. Sham operated rats (G1) and half of hypertensive rats (G2) were studied after 8 weeks. The other half of 8 weeks long hypertensive rats (G3) were treated during 8 weeks with Perindopril in drinking water at a dosage adjusted to maintain blood pressure (BP) measured with tail cuff method under 140 mmHg. The study of each rat included 1) coronary blood flow and resistance measurements under resting conditions and after coronary dilation by carbochrome infusion (9 mg/kg) using left atrial injection of radioactive microspheres (method of Wicker and Tarazi) 2) the study of mechanical performance of the isolated papillary muscle 3) weight of left ventricle after separation of septum and free wall whose subendocardial and subepicardial layers were counted separately. Results (mean +/- SD): (table; see text) MAP: mean pressure. LV/BW: left ventricular mass (mg) per gram of body weight; CR (C): minimal coronary resistance after carbochrome (mmHg/ml/min/100 mg); DL/Dt: peak velocity of shortening at L max preload; Vrelax: peak velocity of relaxation; THR: time of half relaxation; p less than 0.05; p less than 0.01 compared to SHAM. In this model, hypertension induced a 50 p. 100 LVH whose regression was nearly complete after 8 weeks of treatment with Perindopril. Minimal coronary resistance after carbochrome were higher in hypertensive rats compared to sham and return to normal after regression of LVH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of perindopril on left ventricular hypertrophy, coronary reserve and mechanical properties of the papillary muscle of the rat with renovascular arterial hypertension]. 295 35

The binding of tritiated ligands for various opiate receptor subtypes to brain membranes prepared from spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was determined. The density (Bmax) or the apparent dissociation constant (Kd) for the binding of the mu-ligand (naltrexone) and delta-ligand (Tyr-D-Ser-Gly-Phe-Leu-Thr) to brain membranes of hypertensive and normotensive rats did not differ. However, the Bmax for the binding of kappa-ligand (ethylketocyclazocine, EKC) to brain membranes after the suppression of mu and delta-sites by 100 nM each of unlabeled D-Ala2-MePhe4-Gly-ol5-enkephalin and D-Ala2-D-Leu5-enkephalin, respectively, was significantly greater in hypertensive rats compared to normotensive rats. The Kd values for the binding of 3H-EKC in the two groups did not differ. The binding of 3H-EKC in brain regions was in the order: hypothalamus greater than midbrain greater than striatum greater than cortex greater than pons + medulla. The increase in the binding of 3H-EKC in the brain of hypertensive rats compared to normotensive rats was due to increased binding in the hypothalamus and cortex. These results provide for the first time evidence of selective proliferation of kappa-opiate receptors in the brain of hypertensive rats, and suggest that brain kappa-opiate receptors may play an important role in the pathophysiology of hypertension.
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PMID:Selective proliferation of brain kappa opiate receptors in spontaneously hypertensive rats. 302 39

A three-dimensional model of human renin has been constructed based on the assumption that the overall folding of the aspartyl proteases is very similar. As a reference, we used penicillopepsin, the structure of which has been reported at a resolution of 1.8 A, and its main chain was traced to build a model of renin. The resulting structure seems to be stable from the hydrophobic and hydrophilic viewpoints. Comparison of the tertiary structure of human renin with that of penicillopepsin and mouse renin suggests the existence of a high structural homology as well as differences in the molecular geometry of the active sites that may influence the substrate specificity. The asparagine side chains in the glycosidation signal of Asn-X-Thr are exposed on the surface. Moreover, the site in human renin that corresponds to the proteolytic cleavage site in mouse renin also appears to be exposed on the surface so as to be easily scissored during the maturation process. The insertions and deletions of amino acid residues were found to arise on the surface, and in some places they occurred in complementary manners. Models of molecular complexes between human renin and renin inhibitor were constructed to understand the interacting modes that indicate how new renin inhibitors develop. Inhibitor-binding sites were directly assigned based on the models of the inhibitor-enzyme complex.
Hypertension
PMID:Three-dimensional structure of human renin. 388 99


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