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)

1. Previous studies on the pathogenetic mechanisms of hypertension in the Milan hypertensive strain of rat (MHS) showed that a polymorphism within the alpha-adducin gene is responsible for up to 50% of the blood pressure difference between MHS and their MNS normotensive control strain. A case-control study has shown also in humans an association between alpha-adducin locus and hypertension using 4 multiallelic markers surrounding the alpha-adducin locus. 2. With a multiple regression approach we provide an estimate of the contribution of the genotype for each marker to the blood pressure variability in comparison to that provided by sex, body mass index and age. 3. While sex, body mass index and age contributed by about 40-45% to the overall blood pressure variability, the inclusion of the genotype for the marker closer to the alpha-adducin locus provided a further increase of the variability explained of about 5%. 4. The contribution independently provided by the other markers decreased exponentially with the increase of distance from alpha-adducin locus.
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PMID:alpha-adducin may control blood pressure both in rats and humans. 907 48

In Milan hypertensive rats (MHS) the sequence of events going from renal function to cell membrane ion transport abnormalities and finally to the molecular defect responsible of hypertension has been established. A polymorphism of the cytoskeletal protein adducin has been identified as a likely culprit for hypertension in these rats. Two point mutations in MHS alpha- (F316Y) and beta- (Q529R) adducin genes have been shown to be associated with hypertension in genetic crosses of MHS and MNS rats. Also in humans, a polymorphism of alpha-adducin gene (Gly460Trp) has been found to be significantly associated both to hypertension and salt sensitivity. Studies aimed at clarifying the functional role of alpha-adducin variants have shown that adducin from the MHS rats is able to stimulate Na-KATPase activity both after transfection in renal tubular cells and after incubation with the enzyme in a cell-free system. Also the human hypertensive alpha-adducin variant displays the same activity of MHS adducin in a cell-free system. Therefore, both in humans and in rats, adducin polymorphisms may affect blood pressure and kidney function by modulating the overall capacity of tubular epithelial cells to transport ions, through variations of the Na-KATPase activity. However adducin polymorphisms account for only a portion of hypertension both in humans and rats. Therefore additive or epistatic interactions with other genes involved in renal sodium handling need to be studied.
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PMID:Adducin in essential hypertension. 967 91

Endogenous ouabain-like factor (OLF) is present in mammal tissues and after standardized extraction procedure can be similarly quantified by two independent assays: RIA and Na-KATPase inhibition. OLF was quantified both from plasma and tissues obtained from MHS hypertensive and MNS normotensive rats, maintained under the same environmental and dietary conditions, and from plasma of healthy volunteers and essential hypertensive patients. OLF biochemical characterization shows that it behaves like ouabain except for a 1000-fold higher affinity for the ouabain low-affinity Na-KATPase isoforms than ouabain. Tissue and plasma levels of OLF are higher in MHS than in MNS rats and are not influenced by exogenous OLF sources. Plasma OLF is also increased in a subgroup of hypertensive patients. Both in rats and humans a primary cell membrane alteration affecting ion transports seems to be linked to the increased levels of OLF. An antihypertensive compound which selectively antagonizes the pressor effect of OLF and corrects the ion transport defect is under development and can represent a new pharmacological approach to the treatment of hypertension.
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PMID:Role of the ouabain-like factor and Na-K pump in rat and human genetic hypertension. 968 19


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