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 present study describes characteristic features of two clonal subpopulations of opossum kidney (OK) cells (OK(LC) and OK(HC)) that are functionally different but morphologically identical. The most impressive differences between OK(HC) and OK(LC) cells are the overexpression of Na+-K+-ATPase and type 3 Na+/H+ exchanger by the former, accompanied by an increased Na+-K+-ATPase activity (57.6 +/- 5.6 vs. 30.0 +/- 0.1 nmol P(i). mg protein(-1). min(-1)); the increased ability to translocate Na+ from the apical to the basolateral surface; and the increased Na+-dependent pH(i) recovery (0.254 +/- 0.016 vs. 0.094 +/- 0.011 pH units/s). Vmax values (in pH units/s) for Na+-dependent pHi recovery in OK(HC) cells (0.00521 +/- 0.0004) were twice (P < 0.05) those in OK(LC) (0.00202 +/- 0.0001), with similar Km values (in mM) for Na+ (OK(LC), 21.0 +/- 5.5; OK(HC), 14.0 +/- 5.6). In addition, we measured the activities of transporters (organic ions, alpha-methyl-D-glucoside, L-type amino acids, and Na+ and enzymes (adenylyl cyclase, aromatic L-amino acid decarboxylase, and catechol-O-methyltransferase). The cells were also characterized morphologically by optical and scanning electron microscopy and karyotyped. It is suggested that OK(LC) and OK(HC) cells constitute an interesting cell model for the study of renal epithelial physiology and pathophysiology, namely, hypertension.
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PMID:Expression and function of sodium transporters in two opossum kidney cell clonal sublines. 1206 May 89

Genomic loci bearing stress-related phenotypes were dissected in recombinant congenic strains (RCS) of mice with C57BL/6J (B6) and A/J progenitors. Adult male mice from 14 A/J and 22 B6 background lines were evaluated for emotional reactivity in open-field (OF) and elevated plus-maze tests. Core temperature was monitored by radio telemetry during immobilization and on standard as well as salt-enriched diets. In addition, urinary electrolytes were measured. Genome-wide linkage analysis of the parameters revealed over 20 significant quantitative trait loci (QTL). The highest logarithm of odds (LOD) scores were within the previously-reported OF emotionality locus on Chr 1 (LOD = 4.6), in the dopa decarboxylase region on Chr 11 for the plus-maze (LOD = 4.7), and within a novel region of calmodulin 1 on Chr 12 for Ca++ excretion after a 24-h salt load (LOD = 4.6). RCS stress QTL overlapped with several candidate loci for cardiovascular (CV) disease. In silico evidence of functional polymorphisms by comparative sequence analysis of progenitor strains assisted to ascertain this convergence. The anxious BcA70 strain showed down regulation of Atp1a2 gene expression in the heart (P < 0.001) and brain (P < 0.05) compared with its parental B6 strain, compatible with the enhanced emotionality described in knock out animals for this gene, also involved in the salt-sensitive component of hypertension. Functional polymorphisms in regulatory elements of candidate genes of the CV/inflammatory/immune systems support the hypothesis of genetically-altered environmental susceptibility in CV disease development.
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PMID:Genetic determinants of emotionality and stress response in AcB/BcA recombinant congenic mice and in silico evidence of convergence with cardiovascular candidate genes. 1791 2

In addition to its role as an essential neurotransmitter, dopamine serves important physiologic functions in organs such as the kidney. Although the kidney synthesizes dopamine through the actions of aromatic amino acid decarboxylase (AADC) in the proximal tubule, previous studies have not discriminated between the roles of extrarenal and intrarenal dopamine in the overall regulation of renal function. To address this issue, we generated mice with selective deletion of AADC in the kidney proximal tubules (referred to herein as ptAadc-/- mice), which led to selective decreases in kidney and urinary dopamine. The ptAadc-/- mice exhibited increased expression of nephron sodium transporters, decreased natriuresis and diuresis in response to l-dihydroxyphenylalanine, and decreased medullary COX-2 expression and urinary prostaglandin E2 excretion and developed salt-sensitive hypertension. They had increased renin expression and altered renal Ang II receptor (AT) expression, with increased AT1b and decreased AT2 and Mas expression, associated with increased renal injury in response to Ang II. They also exhibited a substantially shorter life span compared with that of wild-type mice. These results demonstrate the importance of the intrarenal dopaminergic system in salt and water homeostasis and blood pressure control. Decreasing intrarenal dopamine subjects the kidney to unbuffered responses to Ang II and results in the development of hypertension and a dramatic decrease in longevity.
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PMID:Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. 2170 Oct 66

We have recently demonstrated that intrarenal dopamine plays an important role in preventing the development of systemic hypertension. Similarly, renal cytochrome P-450 (CYP)-epoxygenase-derived arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), also are antihypertensive through inhibiting sodium reabsorption and vasodilation. The potential interaction between renal dopamine and epoxygenase systems was investigated. Catechol-O-methyl-transferase (COMT)(-/-) mice with increased intrarenal dopamine levels and proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC(-/-)) mice with renal dopamine deficiency were treated with a low-salt diet or high-salt diet for 2 wk. Wild-type or Cyp2c44(-/-) mice were treated with gludopa, which selectively increased renal dopamine levels. In low salt-treated mice, urinary EET levels were related to renal dopamine levels, being highest in COMT(-/-) mice and lowest in ptAADC(-/-) mice. In high salt-treated mice, total EET and individual EET levels in both the kidney and urine were also highest in COMT(-/-) mice and lowest in ptAADC(-/-) mice. Selective increases in renal dopamine in response to gludopa administration led to marked increases in both total and all individual EET levels in the kidney without any changes in blood levels. qRT-PCR and immunoblotting indicated that gludopa increased renal Cyp2c44 mRNA and protein levels. Gludopa induced marked increases in urine volume and urinary sodium excretion in wild-type mice. In contrast, gludopa did not induce significant increases in urine volume or urinary sodium excretion in Cyp2c44(-/-) mice. These studies demonstrate that renal EET levels are maintained by intrarenal dopamine, and Cyp2c44-derived EETs play an important role in intrarenal dopamine-induced natriuresis and diuresis.
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PMID:Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney. 2415 93

Hypertension is one of the most common cardiovascular diseases, resulting in serious complications such as cardiovascular damage and chronic kidney disease. Tianshu capsule (TSC), composed of Chuanxiong (Ligusticum chuanxiong Hort) and Tianma (Gastrodiaelata Blume), has been widely used to treat the blood stasis type of headache and migraine in clinic. Results of previous research showed its antihypertensive effects, but the underlying mechanisms were still unclear. The purpose of this study was to evaluate the antihypertensive effect of TSC on spontaneously hypertensive rats by 1H NMR-based metabonomics and enzyme-linked immunosorbent assay (ELIAS), explore potential biomarkers and targets, and probe the potential mechanism of TSC on antihypertensive treatment. The results showed that TSC could decrease the product of oxidative stress (MDA) and enhance the activities of SOD and GSH-Px, down-regulate the expression of enzymes (LDHA, PKM2 and HK2) related to glycolysis, and perturb the levels of a series of amino acids (isoleucine, alanine, asparagine, citrate, etc.) and pathways. Multivariate statistical analyses showed remarkable changes in some endogenous metabolites after administrating TSC related to oxidative stress, amino acid metabolism and energy metabolism disturbances. Some enzymes (alanine-glyoxylate aminotransferase-2, tyrosine hydroxylase, dopa decarboxylase, etc.) related to metabolic biomarkers were predicted as the potential targets of TSC treatment on SHRs. The discoveries are helpful to understand the antihypertensive mechanism of TSC and provide theoretical evidence for its future research, development and clinical use.
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PMID:Effects of Tianshu Capsule on Spontaneously Hypertensive Rats as Revealed by 1H-NMR-Based Metabolic Profiling. 3157 79


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