ABSTRACT
In the iron-pnictide material CeFeAsO not only the Fe moments, but also the local 4f moments of the Ce order antiferromagnetically at low temperatures. We elucidate on the peculiar role of the Ce on the emergence of superconductivity. While application of pressure suppresses the iron SDW ordering temperature monotonously up to 4 GPa, the Ce-4f magnetism is stabilized until both types of magnetic orders disappear abruptly and a narrow SC dome develops. With further increasing pressure characteristics of a Kondo-lattice system become more and more apparent in the electrical resistivity. This suggests a connection of the emergence of superconductivity with the extinction of the magnetic order and the onset of Kondo screening of the Ce-4f moments.
ABSTRACT
The project DemO3AC (demonstration of large-scale wastewater ozonation at the Aachen-Soers wastewater treatment plant, Germany) of the Eifel-Rur Waterboard contains the construction of a large-scale ozonation plant for advanced treatment of the entire 25 million m³/yr of wastewater passing through its largest wastewater treatment plant (WWTP). In dry periods, up to 70% of the receiving water consists of treated wastewater. Thus, it is expected that effects of ozonation on downstream water biocoenosis will become observable. Extensive monitoring of receiving water and the WWTP shows a severe pollution with micropollutants (already prior to WWTP inlet). (Eco-)Toxicological investigations showed increased toxicity at the inlet of the WWTP for all assays. However, endocrine-disrupting potential was also present at other sampling points at the WWTP and in the river and could not be eliminated sufficiently by the WWTP. Total cell counts at the WWTP are slightly below average. Investigations of antibiotic resistances show no increase after the WWTP outlet in the river. However, cells carrying antibiotic-resistant genes seem to be more stress resistant in general. Comparing investigations after implementation of ozonation should lead to an approximation of the correlation between micropollutants and water quality/biocoenosis and the effects that ozonation has on this matter.
Subject(s)
Ozone/chemistry , Rivers/chemistry , Wastewater/chemistry , Water Pollutants, Chemical/analysis , Water Purification/methods , Water Purification/standards , Drug Resistance, Microbial/drug effects , Drug Resistance, Microbial/genetics , Escherichia coli/drug effects , Escherichia coli/genetics , Germany , Rivers/microbiology , Wastewater/microbiology , Water Pollutants, Chemical/toxicityABSTRACT
We have investigated the electrical double layer (EDL) structure at an interface between ionic liquid (IL) and charged surface using molecular dynamics simulations. We show that for three different models of ILs the EDL restructuring, driven by surface charging, can be rationalized by the use of two parameters--renormalized surface charge (κ) and charge excess in the interfacial layers (λ). Analysis of the relationship between the λ and κ parameters provides new insights into mechanisms of over-screening and charge-driven structural transitions in the EDL in ionic liquids. We show that the restructuring of the EDL upon charging in all three studied systems has two characteristic regimes: (1) transition from the bulk-like (κ(Ion) = 0) to the multilayer structure (κ(Ion) ≈ 0.5) through the formation of an ionic bilayer of counter- and co-ions; and (2) transition from the multilayer (κ(Ion) ≈ 0.5) to the crowded (κ(Ion) > 1) structure through the formation of a monolayer of counter-ions at κ(Ion) = 1.
ABSTRACT
AIM: The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. PATIENTS AND METHODS: For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. RESULTS: No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). CONCLUSION: Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lymphatic Metastasis/pathology , Lymphatic Metastasis/radiotherapy , Male , Multivariate Analysis , Neoplasm Staging , Pneumonectomy , Postoperative Care , Postoperative Complications/etiology , Proportional Hazards Models , Radiation Pneumonitis/etiology , Radiation Pneumonitis/mortality , Radiotherapy Dosage , Radiotherapy, Adjuvant , Retrospective Studies , Young AdultABSTRACT
A reproducible and transparent quality of clinical treatments plays an important role in the performance of a hospital. In liver transplantation (LT), this is particularly important for patient safety, resource planning, documentation, and quality management. Thus, the clinical pathway for LT was documented in an electronic format within our research project PIGE. Data from clinical information systems were linked to this pathway, which allows for process monitoring (the assessment of the current state for every patient in the LT process) and a retrospective analysis of all treatments in addition to all data pertaining to the treatment, for example, cost, time, number of personnel, etc.
Subject(s)
Critical Pathways , Liver Transplantation , Health Care Rationing , Humans , Patient SafetyABSTRACT
AIMS/HYPOTHESIS: Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. METHODS: A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. RESULTS: Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. CONCLUSIONS/INTERPRETATION: Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. TRIAL REGISTRATION: ClincalTrials.gov: NCT00000620. FUNDING: The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.
Subject(s)
Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Fenofibrate/adverse effects , Fenofibrate/therapeutic use , Hypolipidemic Agents/adverse effects , Kidney/drug effects , Aged , Cardiovascular Diseases/blood , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Hypolipidemic Agents/therapeutic use , Male , Middle AgedABSTRACT
Health status is acknowledged by nursing theory as a factor in the probability of health behavior changes. Yet few studies have addressed the health-related barriers encountered by chronically ill elderly patients in primary care clinics who are trying to increase their physical activity. This study used self- and interviewer-administered instruments to assess potential barriers to physical activity in a sample of 60- to 80-year-old patients entering a walking program. Pain, fatigue, and mobility and sensory impairments were prevalent and could be significant barriers to participation. The authors present specific suggestions for helping patients overcome these barriers.
Subject(s)
Activities of Daily Living , Aged/psychology , Attitude to Health , Disabled Persons/psychology , Exercise/psychology , Health Behavior , Health Knowledge, Attitudes, Practice , Health Status , Primary Health Care , Walking/psychology , Aged, 80 and over , Fatigue/complications , Fatigue/psychology , Female , Geriatric Assessment , Home Care Services , Humans , Male , Nursing Assessment , Pain/complications , Pain/psychology , Surveys and QuestionnairesABSTRACT
The allocation of medical resources is often a great concern in the United States. This article discusses a case concerning utility of resources in a patient with a terminal disease. We assert that the goals of treatment tailored to an individual patient should be made at the bedside by a fiduciary (physician) in conjunction with the patient's preferences and values. There is great responsibility in making these decisions and it is critical that they be made at the bedside with the patient and family clearly aware of the goals of treatments and informed of treatment limitations.
Subject(s)
Ethics, Medical , Utilization Review , Adenocarcinoma/therapy , Aged , Aged, 80 and over , Erythrocyte Transfusion , Humans , Male , Medical Futility , Palliative Care , Quality of Life , Stomach Neoplasms/therapyABSTRACT
The reaction of nona-2,7-diyne, deca-2,8-diyne and hex-1-yne with [RuCp(PR3)(MeCN)2]PF6 (R = Cy, Ph, Me) affords, depending on the structure of the alkyne and the substituent of the phosphine ligand, ruthenium metallacyclopentatriene, allyl carbene and/or butadienyl carbene complexes involving either metal-to-ligand-to-metal migration of the phosphine ligand with concomitant C-H activation or a facile 1,2 hydrogen shift.
ABSTRACT
Studies in adults with Hb SC disease suggested that hydroxyurea reduced hemolysis and increased red cell hydration. Because increased hydration should diminish the polymerization tendency of Hb S we hypothesized that hydroxyurea might repair the urine concentration defect of HbSC disease. Eight Hb SC disease patients, aged 10 to 17 years, were given hydroxyurea daily. Maximal urine concentrating ability following overnight fasting and after subcutaneous arginine vasopressin (dDAVP), blood counts, and cell volumes were observed for 12-15 months. All patients had impaired urine concentrating ability prior to hydroxyurea treatment and failed to increase their ability to concentrate urine following treatment (maximum urine concentration after an overnight fast and dDAVP, 520-530 mOsm). Mean corpuscular volume (MCV) and reticulocyte MCV increased after administration of hydroxyurea, and the reticulocyte count and ratio of red cell hemoglobin to reticulocyte hemoglobin fell but there was little change in PCV. Hb F increased substantially in 2 patients but showed little change in the remaining patients. There was no evidence that hydroxyurea was associated with increased urine concentrating ability in children with Hb SC disease. These results may reflect irreversible renal medullary damage prior to beginning treatment or insufficient intensity or duration of treatment.
Subject(s)
Antisickling Agents/administration & dosage , Hemoglobin SC Disease/drug therapy , Hemoglobin SC Disease/physiopathology , Hydroxyurea/administration & dosage , Kidney Concentrating Ability , Adolescent , Adult , Child , Female , Humans , MaleABSTRACT
Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.
Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Hypertension/physiopathology , Natriuresis/drug effects , Peptides/pharmacology , Adrenomedullin , Anesthesia , Animals , Glomerular Filtration Rate/drug effects , Male , Rats , Rats, Inbred SHR , Renal Circulation/drug effectsABSTRACT
The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.
Subject(s)
Endothelins/physiology , Hypertension/physiopathology , Kidney/physiopathology , Sodium, Dietary/administration & dosage , Animals , Hemodynamics , Hypertension/etiology , Indans/pharmacology , Male , Rats , Rats, Sprague-DawleySubject(s)
Hypertension, Renal/etiology , Kidney Failure, Chronic/therapy , Renal Dialysis , Blood Volume/physiology , Body Weight , Humans , Hypertension, Renal/physiopathology , Kidney Failure, Chronic/complications , Water-Electrolyte Imbalance/etiology , Water-Electrolyte Imbalance/physiopathologyABSTRACT
1. According to the renal body fluid feedback mechanism for long-term control, persistent hypertension can only occur as a result of a reduction in renal sodium excretory function or a hypertensive shift in the pressure natriuresis relationship. Although an abnormal relationship between renal perfusion pressure and renal sodium excretion has been identified in every type of hypertension where it has been sought, factors responsible for this effect are still unclear. 2. Nitric oxide (NO) is produced within the kidney and plays an important role in the control of many intrarenal processes that regulate the renal response to changes in perfusion pressure and, thus, help determine systemic vascular volume and blood pressure. Numerous studies have shown that long-term inhibition of NO synthesis results in a chronic hypertensive shift in renal pressure natriuresis. 3. Recent studies have shown that certain animal models of genetic hypertension and forms of human hypertension areas are associated with a decrease in NO synthesis. Reductions in NO synthesis reduce renal sodium excretory function, not only through direct action on the renal vasculature, but through modulation of other vasoconstrictor processes and through direct and indirect alterations in tubular sodium transport. 4. The causes and consequences of the disregulation of NO in hypertension and other renal disease processes remain an important area of investigation.
Subject(s)
Hypertension/physiopathology , Kidney/physiopathology , Nitric Oxide/physiology , Animals , Dogs , Enzyme Inhibitors/pharmacology , Glomerular Filtration Rate/drug effects , Kidney/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Natriuresis/drug effectsABSTRACT
Airway inflammation in children younger than 5 yr of age is difficult to assess, particularly in patients with cystic fibrosis (CF). Furthermore, determining responses to therapies is often subjective in infants, especially those with CF. To determine whether airway DNA levels could be used as an index of airway inflammation, we measured DNA levels in bronchoalveolar lavage fluid (BALF), using a Hoechst dye-binding assay. BALF DNA levels and neutrophils from 16 infants with CF were compared with levels obtained from seven older CF patients and nine control children who underwent bronchoalveolar lavage for evaluation of other pulmonary diseases. BALF DNA was increased in both infants (3.2 +/- 0.7 microg/ml) and older patients with CF (5.4 +/- 0.9 microg/ml) compared with the controls (0.7 +/- 0.2 microg/ml) (mean +/- SEM). BALF DNA levels were not significantly different between infants and older patients with CF. BALF neutrophil counts in CF patients were significantly higher than in controls. Furthermore, BALF DNA levels and total neutrophil counts in infants with CF correlated positively with one another. We conclude that: (1) DNA levels were easily quantifiable in BALF of young children; (2) DNA levels in BALF from CF patients were greater than in a group of children with other pulmonary diseases, and that in some infants with CF, BALF DNA levels were equivalent to those of much older patients with CF; (3) DNA levels in BALF correlate with BALF neutrophil number, an index of inflammation; and (4) some infants with CF have increased levels of DNA in BALF, which may justify a clinical trial of aerosolized rhDNase in this population.
Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Cystic Fibrosis/metabolism , DNA/isolation & purification , Lung Diseases/metabolism , Neutrophils , Adult , Bronchoalveolar Lavage Fluid/microbiology , Child, Preschool , Cystic Fibrosis/blood , Cystic Fibrosis/microbiology , Humans , Infant , Leukocyte Count , Lung Diseases/blood , Lung Diseases/microbiologyABSTRACT
1. Chronic Na+, K(+)-ATPase inhibition with ouabain induces hypertension in the rat. To examine the role of the kidney in this process, the effect of changes in renal perfusion pressure on glomerular filtration rate, renal blood flow and urinary sodium excretion were determined in rats treated intraperitoneally with ouabain (27.8 micrograms day-1 kg-1 body weight) or vehicle for 6 weeks. 2. After ouabain administration, baseline mean arterial pressure was significantly higher (P < 0.05) in ouabain-treated rats (151 +/- 2 mmHg; n = 9) than in control rats (116 +/- 4 mmHg; n = 8). 3. At equivalent renal perfusion pressures, glomerular filtration rate was significantly lower (P < 0.05) in ouabain-treated rats compared with control rats. Glomerular filtration rate was 721 +/- 73 microliters/min at 150 mmHg, and fell significantly to 322 +/- 64 microliters/min at 100 mmHg. In the control group, glomerular filtration rate was well autoregulated. The glomerular filtration rate autoregulatory index was calculated to determine the ability to maintain glomerular filtration rate during changes in renal perfusion pressure (0 reflects perfect autoregulation; > 1 reflects the absence of autoregulation). This index was greater in the ouabain group than in the control group (1.54 +/- 0.2 compared with 0.29 +/- 0.2; P < 0.05). Renal blood flow showed a similar pattern. 4. Absolute urinary sodium excretion rate was less in ouabain-treated rats than in control rats at equivalent renal perfusion pressures. The slope of the relationship between absolute urinary sodium excretion rate and renal perfusion pressure was greater (P < 0.05) in the control group than in the ouabain group (309.1 +/- 57.1 compared with 82.1 +/- 14.8 mumol min-1 mmHg-1). 5. Thus, chronic inhibition of Na+,K(+)-ATPase induces less efficient autoregulation of glomerular filtration rate and renal blood flow as well as a rightward shift in the pressure natriuresis relationship, such that a 25-30 mmHg higher renal perfusion pressure is necessary to excrete any given sodium load. These abnormalities may contribute to the development and maintenance of hypertension in this model.
Subject(s)
Hypertension, Renal/physiopathology , Kidney/physiopathology , Ouabain/pharmacology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Glomerular Filtration Rate/drug effects , Homeostasis/drug effects , Kidney/drug effects , Male , Natriuresis/drug effects , Rats , Rats, Sprague-Dawley , Renal Circulation/drug effectsABSTRACT
Although it has been reported that Na+,K+-ATPase inhibition with bufalin induces acute and chronic hypertension in the rat, the mechanisms mediating this response are unclear. To examine the role of the kidney in this process, glomerular filtration rate, renal blood flow, and pressure natriuresis were determined in rats treated with bufalin or vehicle during changes in renal perfusion pressure. Mean arterial pressure increased from 123 +/- 4 to 149 +/- 3 mm Hg (P < .05) after 40 minutes of intravenous bufalin and remained at this level. In control rats, glomerular filtration rate was well autoregulated. In bufalin-treated rats, glomerular filtration rate fell with decreasing renal perfusion pressure. Glomerular filtration rate autoregulatory index was greater in bufalin-treated than control rats (P < .05). Renal blood flow showed a similar pattern. Urine flow and sodium excretion were less in bufalin-treated than control rats at equivalent renal perfusion pressures. The slope of the line describing the relation between urine flow and renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Similarly, the slope of the line relating sodium excretion to renal perfusion pressure was greater (P < .05) in control than bufalin-treated rats. Thus, acute increases in blood pressure during Na+, K+-ATPase inhibition are associated with impaired renal autoregulation and pressure natriuresis. This effect may be important in chronic hypertension associated with Na+,K+-ATPase inhibition in the rat.
Subject(s)
Bufanolides/administration & dosage , Hypertension/physiopathology , Natriuresis/drug effects , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Animals , Blood Pressure/drug effects , Glomerular Filtration Rate/drug effects , Hypertension/chemically induced , Hypertension/enzymology , Male , Rats , Rats, Sprague-Dawley , Regional Blood Flow/drug effectsABSTRACT
Calcium supplementation prevents hypertension in Dahl S (DS) rats. Because abnormal pressure natriuresis may contribute to the development of hypertension, we examined the effect of calcium on pressure natriuresis. DS and Dahl R (DR) rats maintained on a 4% sodium diet containing either 0.5% or 2% calcium for 4 weeks were anesthetized; sodium excretion, renal blood flow, and inulin clearance were determined at perfusion pressures of 100, 125, and 156 mm Hg. Inulin clearance and renal blood flow were not different between groups. Sodium excretion increased with increasing renal perfusion pressure in all groups. The slope of the line relating renal perfusion pressure to sodium excretion was greater (P < .05) in DR rats than in DS rats on normal calcium intakes. High calcium intake normalized the slope of the line relating renal perfusion pressure to sodium excretion in DS rats, but had no effect on DR rats. Thus, dietary calcium supplementation normalizes the blunted pressure natriuresis response in the DS rat and may contribute to the prevention of hypertension.
Subject(s)
Blood Pressure/drug effects , Calcium, Dietary/pharmacology , Natriuresis/drug effects , Anesthesia , Animals , Calcium/urine , Diet , Kidney/drug effects , Male , Organ Size/drug effects , Rats , Rats, Inbred Strains , Regional Blood Flow/drug effects , Renal Circulation/drug effects , Sodium, Dietary/adverse effects , Urodynamics/drug effectsABSTRACT
Hypertension in the spontaneously hypertensive rat (SHR) is associated with reduced renal excretory function, low renal plasma flow, reduced glomerular filtration rate, and reduced renal interstitial hydrostatic pressure. The mechanisms responsible for these abnormalities in renal function are unknown. The purpose of this study was to determine the role of intrarenal endothelin in altering renal hemodynamic and excretory function in the SHR. Both PD 145065 (an endothelin A and B receptor antagonist) and FR 139317 (a selective endothelin A receptor antagonist) or saline was infused into the renal interstitium of 14- to 16-week-old SHR (n = 7) and age-matched Wistar-Kyoto rats (WKY) (n = 7). Renal perfusion pressure in some SHR was reduced to that of the WKY by a servocontrol system. At a renal perfusion pressure of 124 +/- 4 mm Hg, infusion of PD 145065. (0.03 mg.kg-1.min-1) and FR 139317 (0.02 mg.kg-1.min-1) significantly increased glomerular filtration rate (delta 22%), renal plasma flow (delta 37%), and renal interstitial hydrostatic pressure (from 3.2 +/- 0.5 to 5.4 +/- 0.6 mm Hg) in the SHR. These changes were associated with significant increases in urine flow, absolute sodium excretion, and fractional excretion of sodium. Similar improvements in renal plasma flow, renal interstitial hydrostatic pressure, and renal excretory function were obtained in the SHR whose renal perfusion pressure was not reduced (n = 7). Renal interstitial infusion of endothelin receptor antagonists had no effect on renal hemodynamic or excretory function in the WKY. These data demonstrate that endothelin receptor blockade within the kidney improves renal hemodynamic and excretory function in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)