Biomedical subjects

Sharma Prabhakar

Publications and source records attributed to Sharma Prabhakar.

4 recordsLinked to original sources

PubMed2006

Endothelin-induced increased nitric oxide mediates augmented distal nephron acidification as a result of dietary protein.

Tested was the hypothesis that enhanced nitric oxide (NO) production that is stimulated by increased renal endothelin activity mediates decreased distal nephron HCO(3) secretion that is induced by dietary protein. Munich-Wistar rats that ate minimum electrolyte diets with 50% casein-provided protein (HiPro) compared with controls that ate 20% protein for 3 wk had higher urine excretion of endothelin-1 (80 +/- 15.7 versus 29 +/- 3.9 fmol/kg body wt per d; P < 0.02) and of the NO metabolites NO(2)/NO(3) (21.2 +/- 1.9 versus 14.9 +/- 0.8 mumol/kg body wt per d; P < 0.03). Bosentan, an endothelin A/B receptor antagonist, reduced HiPro rats' urine excretion of net acid (5859 +/- 654 versus 8017 +/- 1103 micromol/d; P < 0.03, paired t test) and NO(2)/NO(3) (18.1 +/- 1.1 versus 22.9 +/- 2.0 micromol/kg body wt per d; P < 0.05, paired t test). N-nitro-l-arginine methyl ester (L-NAME), an NO synthase inhibitor, also decreased urine net acid excretion (6621 +/- 717 versus 8449 +/- 1086 micromol/d; P < 0.05, paired t test) but was not additive to bosentan. L-NAME increased in situ late distal nephron HCO(3) delivery in HiPro rats (18.8 +/- 1.7 versus 9.6 +/- 1.4 pmol/mm per min; P < 0.001) that was mediated by increased distal nephron HCO(3) secretion (-7.2 +/- 0.7 versus -3.5 +/- 0.4 pmol/mm per min; P < 0.001) without changes in distal nephron transtubule HCO(3) permeability or H(+) secretion. Bosentan decreased H(+) secretion and increased HCO(3) secretion in the distal nephron of HiPro rats, but L-NAME had no additive effect on either component. The data support that dietary protein augments distal nephron acidification through decreased HCO(3) secretion that is mediated through endothelin-stimulated NO.

Animals↗

PubMed2006

Lipids and diabetic nephropathy.

Although several factors may mediate the development and progression of diabetic nephropathy, hyperlipidemia is now considered an independent and major determinant of progression of renal disease in diabetes. The following discussion focuses on the experimental evidence that incriminates hyperlipidemia as a pathogenic factor for diabetic nephropathy and the potential mechanisms that may mediate renal injury from hyperlipidemia, as well as the clinical studies involving therapeutic interventions for hyperlipidemia and their impact on progression of diabetic renal disease.

Angiotensin II↗

PubMed2006

Exhaled nitric oxide in asthma: variability, relation to asthma severity, and peripheral blood lymphocyte cytokine expression.

Exhaled nitric oxide has been used as a means of indirectly measuring the underlying inflammation in asthma. The objectives of the study were to measure exhaled nitric oxide levels in asthma patients and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between exhaled nitric oxide and intracellular cytokine expression. Exhaled nitric oxide was elevated in patients with moderate to severe asthma and with treatment decreased in the first week reaching to a near normal level by 4 weeks. Elevated exhaled nitric oxide was associated with decreased IL-4 and IL-13 cytokine expression by CD8 lymphocytes.

Adult↗

PubMed2005

Hyperuricemia induces endothelial dysfunction.

BACKGROUND: Hyperuricemia has been linked to cardiovascular and renal diseases, possibly through the generation of reactive oxygen species (ROS) and subsequent endothelial dysfunction. The enzymatic effect of xanthine oxidase is the production of ROS and uric acid. Studies have shown that inhibiting xanthine oxidase with allopurinol can reverse endothelial dysfunction. Furthermore, rat studies have shown that hyperuricemia-induced hypertension and vascular disease is at least partially reversed by the supplementation of the nitric oxide synthase (NOS) substrate, L-arginine. Therefore, we hypothesized that uric acid induces endothelial dysfunction by inhibiting nitric oxide production. METHODS: Hyperuricemia was induced in male Sprague-Dawley rats with an uricase inhibitor, oxonic acid, by gavage; control rats received vehicle. Allopurinol was placed in drinking water to block hyperuricemia. Rats were randomly divided into four groups: (1) control, (2) allopurinol only, (3) oxonic acid only, and (4) oxonic acid + allopurinol. Rats were sacrificed at 1 and 7 days, and their serum analyzed for serum uric acid and nitrites/nitrates concentrations. The effect of uric acid on nitric oxide production was also determined in bovine aortic endothelial cells. RESULTS: Oxonic acid induced mild hyperuricemia at both 1 and 7 days (P < 0.05). Allopurinol reversed the hyperuricemia at 7 days (P < .001). Serum nitrites and nitrates (NO(X)) were reduced in hyperuricemic rats at both 1 and 7 days (P < .001). Allopurinol slightly reversed the decrease in NO(X) at 1 day and completely at 7 days (P < .001). There was a direct linear correlation between serum uric acid and NO(X) (R(2)= 0.56) and a trend toward higher systolic blood pressure in hyperuricemic rats (P= NS). Uric acid was also found to inhibit both basal and vascular endothelial growth factor (VEGF)-induced nitric oxide production in bovine aortic endothelial cells. CONCLUSION: Hyperuricemic rats have a decrease in serum nitric oxide which is reversed by lowering uric acid levels. Soluble uric acid also impairs nitric oxide generation in cultured endothelial cells. Thus, hyperuricemia induces endothelial dysfunction; this may provide insight into a pathogenic mechanism by which uric acid may induce hypertension and vascular disease.

Animals↗