Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine

Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine. The effects of a calcium antagonist on the response to a loop diuretic were tested in eight hypertensive patients while they received 120mmol · 24hr-1 of dietary Na. Nitrendipine (N; 20 mg) or placebo (P) was administered twice daily for five days and bumetanide (B; 1 mg, i.v.) for the last three days of each period. Cardiac index (CI) was measured during tilt. B alone significantly (P < 0.05; N = 7) reduced CI and increased total peripheral resistance; N prevented these effects of B. Neither drug altered BP consistently. Although three days of B increased plasma renin activity (PRA) during P and N, it increased plasma aldosterone (PAldo) only during P (P, 4.4 ± 1.3 to 7.6 ± 1.0; P < 0.05. N, 5.7 ± 1.3 to 6.0 ± 1.3; pg · liter-1; NS). B increased Na excretion without changing GFR or RPF; this was followed by 18 hours of decreased renal Na excretion. These actions were unchanged by N. N did not change the cumulative excretion of B (P, 268 ± 35 vs. N, 217 ± 21 µg) or the relationship between Na excretion and the log of B excretion. However, Na excretion was increased (P < 0.05) by 40 to 60% in the six hour period following the first two doses of N. Therefore, the cumulative Na balance was more negative during five days of N (P, -47 ± 17 vs. N, -108 ± 24 mmol; P < 0.05). The effect of N and B on Na balance were independent. In conclusion, short-term administration of N: 1) increases CI and reduces TPRI in the post-diuretic state; 2) blunts B-induced increase in PAldo without modifying the rise in PRA; 3) does not change B kinetics or dynamics or the post-diuretic period of renal Na retention; 4) causes negative Na balance which is additive with that produced by B

Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB

Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB.BackgroundAngiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus (DM).MethodsAfter two weeks of streptozotocin-induced DM, rats received either no treatment, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for two weeks. At four weeks, renal expression of the p47phox component of NAD(P)H oxidase, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and nitrotyrosine were evaluated by Western blot and immunohistochemistry and related to plasma lipid peroxidation products (LPO), hydrogen peroxide production in the kidney and 24-hour protein excretion.ResultsImmunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO, renal hydrogen peroxide production and nitrotyrosine deposition. Expression of nNOS was unaltered. Treatment with either ACEI or ARB prevented all these findings and also prevented significant microalbuminuria. The treatments did not affect the elevated blood sugar, nor did DM or its treatment affect the blood pressure or the creatinine clearance.ConclusionEarly proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM

Investigating strength and range of motion of the hip complex in ice hockey athletes

CONTEXT: Ice hockey athletes frequently injure the hip complex via a non-contact mechanism. We investigated patterns of strength and range of motion (ROM) to establish major differences compared to soccer athletes. Soccer athletes were compared to ice hockey athletes due to similarities between the two sports with regards to the intermittent nature and high number of lower limb injuries. OBJECTIVE: To compare the differences in ROM and strength of the hip for both the dominant (Dom) and non-dominant (Ndom) limb in ice hockey and soccer athletes. DESIGN: Case control study. SETTING: Bilateral ROM in hip flexion in sitting (FS) and lying (FL), extension, abduction, adduction, and internal rotation (IR) and external rotation (ER) was measured using a goniometer and assessed for strength using a hand held dynamometer on both the Dom and Ndom limbs. Participants. Twenty four male, active, uninjured NCAA division III ice hockey (16) and soccer (8) athletes. MAIN OUTCOME MEASURE: ROM and strength for hip FS, FL extension, abduction, adduction, IR and ER. A mixed model ANOVA was used to investigate interactions and main effects. RESULTS: Ice hockey athletes exhibited greater hip adduction ROM compared to soccer athletes in the Dom leg (both p=0.002) and when both limbs were combined (p = 0.010). Ice hockey athletes had less ROM in ER (p = 0.042) than soccer athletes. Ice hockey athletes displayed less strength in adduction in their Ndom leg compared to their Dom leg (p=0.02) along with less adduction than soccer players in their Ndom leg (p=0.40). Ice hockey athletes displayed less strength in hip adduction (p=0.030), FS (p=0.023) and FL (p=0.030) than soccer athletes. CONCLUSIONS: Our findings suggest that ice hockey athletes may present an 'at risk' profile for non-contact hip injuries, in comparison with soccer athletes with regards to strength and ROM of the hip

Sodium and Fluid Excretion With Torsemide in Healthy Subjects is Limited by the Short Duration of Diuretic Action

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142477/1/jah32580_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142477/2/jah32580.pd

Regulation of fluid reabsorption in rat or mouse proximal renal tubules by asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase 1

Nitric oxide prevents hypertension yet enhances proximal tubule Na+ reabsorption. Nitric oxide synthase is inhibited by asymmetric dimethylarginine (ADMA) that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) whose type 1 isoform is expressed abundantly in the proximal tubule (PT). We hypothesize that ADMA metabolized by DDAH-1 inhibits fluid reabsorbtion (Jv) by the proximal tubule. S2 segments of the PT were microperfused between blocks in vivo to assess Jv in anesthetized rats. Compared with vehicle, microperfusion of ADMA or Nω-nitro-l-arginine methyl ester (l-NAME) in the proximal tubule reduced Jv dose dependently. At 10−4 mol/l both reduced Jv by ~40% (vehicle: 3.2 ± 0.7 vs. ADMA: 2.1 ± 0.5, P &lt; 0.01 vs. l-NAME: 1.9 ± 0.4 nl·min−1·mm−1, P &lt; 0.01; n = 10). Selective inhibition of DDAH-1 in rats with intravenous L-257 (60 mg/kg) given 2 h before and L-257 (10−5 mol/l) perfused in the proximal tubule for 5 min reduced Jv by 32 ± 4% (vehicle: 3.2 ± 0.5 vs. L-257: 2.2 ± 0.5 nl·min−1·mm−1; P &lt; 0.01) and increased plasma ADMA by ≈50% (vehicle: 0.46 ± 0.03 vs. L-257: 0.67 ± 0.03 µmol/l, P &lt; 0.0001) without changing plasma symmetric dimethylarginine. Compared with nontargeted control small-interference RNA, knock down of DDAH-1 in mice by 60% with targeted small-interference RNAs (siRNA) reduced Jv by 29 ± 5% (nontargeted siRNA: 2.8 ± 0.20 vs. DDAH-1 knockdown: 1.9 ± 0.31 nl·min−1·mm−1, P &lt; 0.05). In conclusion, fluid reabsorption in the proximal tubule is reduced by tubular ADMA or by blocking its metabolism by DDAH-1. L-257 is a novel regulator of proximal tubule fluid reabsorption

Effects of NADPH oxidase inhibitor in diabetic nephropathy

Effects of NADPH oxidase inhibitor in diabetic nephropathy.BackgroundWe used apocynin to test the hypothesis that superoxide anion (O−2) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat.MethodsRats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin.ResultsDM increased excretion of hydrogen peroxide (H2O2), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H2O2, LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion.ConclusionActivation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria

Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis

Background: Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. Methods: Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks. Phosphate (P) binders were discontinued on admission. Patiromer, 12.6 g daily (divided 4.2 g TID with meals), was started on the Monday morning following the last pretreatment week blood sampling. Serum and 24-hour stool samples were collected daily. Results: Mean ± SE serum K decreased (maximum change per corresponding day, 0.6 ± 0.2 mEq/l, p = 0.009) and fecal K increased 58% on patiromer compared with the pretreatment week. During the pretreatment week, 69.0, 47.6, and 11.9% of patients' serum K values were ≥5.5, ≥6.0, and ≥6.5 mEq/l, respectively. This was reduced to 38.1% (p = 0.009), 11.9% (p < 0.001), and 2.4% (p = 0.2) on patiromer. Following P binder discontinuation, the long interdialytic interval mean ± SE serum P numerically increased from 5.8 ± 0.4 to 7.0 ± 0.5 mg/dl (p = 0.06). On patiromer, P decreased from 7.0 ± 0.5 to 6.2 ± 0.5 mg/dl (p = 0.04). While on patiromer, fecal P numerically increased by 112 ± 72 mg/day (17%; p = 0.1792; range -148 to 344 mg/day). No patient discontinued patiromer because of adverse events (AEs); none had serious AEs. Conclusions: In 6 hyperkalemic HD patients, patiromer decreased serum K and P levels and increased fecal K

Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat

Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat.IntroductionTempol is a permeant nitroxide superoxide dismutase (SOD) mimetic that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats (SHRs). We investigated the hypothesis that the antihypertensive response entails a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1 (ET-1), or catecholamines or correction of oxidative stress as indexed by 8-isoprostane prostaglandin F2α (PGF2α) (8-Iso).MethodsGroups (N = 6 to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min) or given tempol (2 mmol/L) in drinking water.ResultsTempol infusion reduced the MAP of anesthetized SHRs (150 ± 5 vs. 126 ± 6mm Hg) (P < 0.005). Oral tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23 ± 6mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion increased the PRA (2.2 ± 0.2 vs. 5.0 ± 0.9 ng/mL/hour) (P < 0.005), did not change excretion of nitric oxide (NO) [NO2 + NO3 (NOx)], ET-1, or catecholamines but reduced excretion of 8-Iso (13.2 ± 1.4 vs. 9.6 ± 0.9 ng/24 hours; P < 0.01). Cumulative Na+ balance and gain in body weight were unaltered by tempol infusion. Tempol prevented a rise in MAP with high salt intake.ConclusionTempol corrects hypertension without a compensatory sympathoadrenal activation or salt retention. The response is independent of nitric oxide, endothelin, or catecholamines and occurs despite increased PRA. It is accompanied by a reduction in oxidative stress and is maintained during increased salt intake

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7+/-11.7 and 42.4+/-12.2, respectively. Significant (P \u3c 0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P \u3c 0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses