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 selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with [3H]rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide (zero carbon spacer arm; rau-AMPC) exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, 125I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). 125I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-azido-3-[125I]iodophenyl) carboxamide (125I-rau-AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both 125I-rau-AMPC and the photolabile arylazide derivative, 125I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2-adrenergic receptors.
Hypertension 1987 Jun
PMID:Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors. 288 70

In both humans and experimental animals, mineralocorticoid (MC)-induced hypertension is associated with myocardial fibrosis. We have shown that this fibrous tissue response includes a reactive interstitial fibrosis not initiated by parenchymal cell loss, and a reparative fibrosis or scarring, occurring in response to cardiac myocyte necrosis. The reactive fibrosis is thought to be related to MC excess, while cell loss and microscopic scarring may be secondary to enhanced potassium excretion or a cytotoxic effect of aldosterone. This histologic study was undertaken to determine whether or not the potassium sparing diuretic amiloride would be effective in preventing the appearance of either form of fibrosis. Uninephrectomized male Sprague Dawley rats received either aldosterone (AL; 0.75 microgram/h), amiloride (AMC; 1 mg/kg/day), aldosterone+amiloride (ALAM), or vehicle (ALC) alone via subcutaneous osmotic minipumps for 8 weeks. All rats received 1% NaCl in their drinking water. Hearts were recovered, immersion-fixed, and tissue sections from both left and right ventricles stained with the collagen specific stain Sirius Red F3BA were morphometrically analyzed. The interstitial collagen volume fraction was elevated in AL and ALAM groups compared to ALC and AMC, but did not differ between AL and ALAM. Microscopic scarring, found in both ventricles, was evident in AL animals, but was not found in the ALAM, AMC, or ALC groups. These data suggest that chronic elevations in plasma aldosterone, relative to dietary sodium intake, do not have a direct cytotoxic effect on cardiac myocytes, but they are associated with a reactive interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride. 834 31

Obese people are at high risk for developing diabetes, dyslipidemia, hypertension, and cardiovascular diseases, which lead to an increased risk of mortality. Activated polymorphonuclear neutrophils (PMN) generate extremely high amounts of reactive oxygen species (ROS), but these are normally targeted at pathogens inside intracellular phagosomes. These same beneficial antimicrobial functions can cause significant local tissue injury and lead to the development of pathologic systemic inflammatory conditions. PMN apoptosis is a major mechanism associated with the resolution of inflammatory reactions. The goals of the present study were: 1) to evaluate the level of reactive oxygen species production in PMN from obese people before and during body mass reduction, 2) to investigate the in vitro effect of flavonoids: quercetin and rutin on oxidative metabolism and apoptosis of stimulated neutrophils in obese patient. We tested 30 obese patients (women) before body mass reduction and 20 patients during low calories diet. The inclusion criteria were based on physical examination, BMI, WHR, the body composition examination based on bioimpedance method and biochemical assessment. PMN were isolated and oxidant production, in response to 1 microg/ml PMA, was characterised by the production of hydrogen peroxide, nitric oxide and chemiluminescence intensity. Caspase-3 activation was assayed by the method of DEVD-AMC cleavage in PMN cultured up to 24 hours. The results of our study showed: 1) the decrease in PMN oxidant production in patient during the mass reduction, 2) the strong antioxidant activity of quercetin and rutin in obese patients before and during the body mass reduction, these effects were dose dependent and rutin was less potent than quercetin, 3) acceleration of PMN apoptosis by rutin is associated with an increase in caspase 3 activity.
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PMID:[Oxidative metabolism of neutrophils in obese patients before and during body mass reduction: the in vitro effect of quercetin and rutin]. 1612 80