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D Arsenault

Publications and source records attributed to D Arsenault.

5 recordsLinked to original sources
PubMed2006

Triple VPI CGS 35601 reduces high blood pressure in low-renin, high-salt Dahl salt-sensitive rats.

We previously reported that CGS 35601, a potent triple inhibitor of angiotensin-converting enzyme, neutral endopeptidase, and endothelin-converting enzyme 1, completely normalized mean arterial blood pressure (MABP) in 36-week-old spontaneously hypertensive rats, a normal renin model. The aim of the present study was to determine the effects of this triple vasopeptidase inhibitor (VPI) on the hemodynamic profile of instrumented, conscious, and unrestrained Dahl salt-sensitive (DSS) rats, a gene-prone, high-salt diet-induced low-renin hypertension model. Male DSS rats (mean weight [+/-SEM], 385 +/- 10 g) were fed a normal diet (Group 1) or a high-salt diet (Groups 2 and 3; 8% NaCl in food) for 6 weeks and then instrumented with a carotid catheter and placed individually in metabolic cages for 30 days. The hemodynamic, hematological, and biochemical profiles were assessed daily. Dose-dependent treatment started after a 7-day stabilization period in Groups 1 and 2 (vehicle dosage, 250 microl/hr) and Group 3 (CGS 35601 dosages of 0.1, 1, and 5 mg/kg/day for 6 days per dose by means of constant intra-arterial infusion), followed by a 5-day washout period. Two additional groups included normotensive Wistar rats (Group 4) and DSS rats that received a double high-salt solid (8% NaCl) and liquid (1% NaCl) diet (Group 5). The MABP in rats receiving CGS 35601 decreased in a dose-dependent fashion toward the baseline level observed in DSS rats receiving a normal diet. The heart rate was unaffected. The hemodynamic profile returned to normal during the washout period. This novel triple VPI is a potent and effective antihypertensive agent with a safe short-term profile that may be of interest for treating hypertension and other cardiovascular diseases. Other hypertensive rat models are being tested.

Animals↗
PubMed1998

Immunohistochemical localization of nephrocalcin, a kidney-specific glycoprotein, to renal cell carcinoma.

OBJECTIVES: Nephrocalcin (NC), an acidic glycoprotein produced by renal proximal tubule cells and functioning as an inhibitor of calcium oxalate monohydrate crystalization, has been previously shown to have increased urinary excretion in patients with renal cell carcinoma (RCC). The current study uses immunohistochemical techniques to localize NC to cells of primary RCC. METHODS: We studied 29 kidneys removed because of RCC. Slides were deparaffinized and stained after incubating with anti-NC antibody by using the avidin-biotin-peroxidase complex techniques. Uptake of stain by tumor cells and adjacent normal renal cells was compared. RESULTS: Twenty-seven kidneys (93%) showed positive staining for RCC tumor cells; 2 kidneys staining positive for normal proximal tubule cells failed to stain adjacent RCC tumor cells (7%). CONCLUSIONS: The data suggest that enhanced production of urinary NC in patients with RCC derives from cells of the primary tumor.

Adolescent↗
PubMed1998

Contribution of human uropontin to inhibition of calcium oxalate crystallization.

Uropontin (UP) is known to inhibit the growth and nucleation of calcium oxalate monohydrate (COM) crystals, and it also impedes attachment of calcium oxalate crystals to cultured renal epithelial cells. However, its role in normal defense against renal crystallization, and in pathogenesis of nephrolithiasis is unclear. In this study we determined the effect of UP on aggregation of COM crystals as well as the inhibitory activity of UP on COM crystal growth and nucleation in a series of normal subjects, in order to assess the potential of UP as an important urinary inhibitor. The mean urinary excretion of UP measured by ELISA was 185 +/- 12 nmol/24 hr (mean +/- SEM) with a mean urine UP concentration of 131 +/- 13 nM. Uropontin isolated by immunoaffinity chromatography was a very potent inhibitor of COM crystal aggregation, with a mean UP concentration of 28 +/- 4 nM required for a 50% reduction in aggregation. The kDa for COM crystal growth inhibition determined from Langmuir type isotherms was 21 +/- 3 nM and the concentration required for 50% reduction in COM crystal growth rate was 16 +/- 2 nM. Inhibition of secondary nucleation was measured at a single concentration of 200 nM, which reduced the nucleation rate to 42 +/- 3% of control. Using a theoretical model of growth and aggregation inhibition at varying urine flow rates, we showed that inhibitory activity of UP would be significant for all subjects over a wide range of urine flow rates. Overall, UP is a potent inhibitor of COM aggregation as well as growth and nucleation. The urinary concentration of UP is in the range in which its contribution to inhibition of growth and aggregation are likely to be substantial. Thus, UP appears to be an important natural defense against renal crystallizations and nephrolithiasis.

Adult↗