Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects: a double-blind, placebo-controlled, multicenter trial.

Prostaglandins of the E series (PGE) are known to contribute to the maintenance of renal hemodynamics in subjects with chronic renal insufficiency. Agents that block PGE synthesis, nonsteroidal anti-inflammatory agents (NSAID), are widely used by people with renal insufficiency. This study was undertaken in subjects with renal insufficiency secondary to diabetes to evaluate the acute effects of a PGE1 analog, misoprostol, on NSAID-induced changes in RBF, as calculated by para-aminohippurate clearance, and GFR, as calculated by inulin clearance. Sodium excretion was also assessed. Twenty-five fasting subjects with a mean age of 56 +/- 4 yr received 800 mg of ibuprofen orally. A concomitant dose of either a placebo (PL) or 200 micrograms of misoprostol was also given. This was followed in 1 h by either a placebo or an additional 200-micrograms dose of misoprostol. Measurements for the determination of RBF, GFR, blood pressure, and fractional excretion of sodium were performed every 30 min for the next 5 h. The greatest reduction in both GFR (-25 +/- 7 mL/min per 1.73 m2 PL versus -10 +/- 4 mL/min per 1.73 m2, misoprostol delta GFR; P < 0.05) and RBF (-48 +/- 21 mL/min per 1.73 m2 PL versus -15 +/- 8 mL/min per 1.73 m2, M delta RBF; P < 0.05) occurred approximately 2 h after the NSAID dose. No significant differences were noted in blood pressure, fractional excretion of sodium, or other measured parameters between groups during the entire study. Gastrointestinal upset was the most common side effect observed in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO

AJP Renal Physiology ◽

10.1152/ajprenal.00410.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. F1260-F1266 ◽

Cited By ~ 6

Author(s):

Xuming Sun ◽

Ellen Tommasi ◽

Doris Molina ◽

Renu Sah ◽

K. Bridget Brosnihan ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Fractional Excretion ◽

Urine Osmolality ◽

Brain Regions ◽

Lower Blood Pressure ◽

Angiotensin Ii Receptor ◽

Lower Blood ◽

Fractional Excretion Of Sodium ◽

The Impact

Diets rich in grains and meat and low in fruits and vegetables (acid-producing diets) associate with incident hypertension, whereas vegetarian diets associate with lower blood pressure (BP). However, the pathways that sense and mediate the effects of acid-producing diets on BP are unknown. Here, we examined the impact of the deletion of an acid sensor GPR4 on BP. GPR4 is a proton-sensing G protein-coupled receptor and an acid sensor in brain, kidney, and blood vessels. We found that GPR4 mRNA was higher in subfornical organ (SFO) than other brain regions. GPR4 protein was abundant in SFO and present in capillaries throughout the brain. Since SFO partakes in BP regulation through the renin-angiotensin system (RAS), we measured BP in GPR4−/− and GPR4+/+ mice and found that GPR4 deletion associated with lower systolic BP: 87 ± 1 mmHg in GPR4−/− ( n = 35) vs. 99 ± 2 mmHg ( n = 29) in GPR4+/+; P < 0.0001, irrespective of age and sex. Angiotensin II receptors detected by 125I-Sarthran binding were lower in GPR4−/− than GPR4+/+ mice in SFO and in paraventricular nucleus of hypothalamus. Circulating angiotensin peptides were comparable in GPR4−/− and GPR4+/+ mice, as were water intake and excretion, serum and urine osmolality, and fractional excretion of sodium, potassium, or chloride. A mild metabolic acidosis present in GPR4−/− mice did not associate with elevated BP, implying that deficiency of GPR4 may preclude the effect of chronic acidosis on BP. Collectively, these results posit the acid sensor GPR4 as a novel component of central BP control through interactions with the RAS.

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Comparison of 24-Hour Ambulatory Central Blood Pressure Reduction Efficacy Between Fixed Amlodipine or Up-Titrated Hydrochlorothiazide Plus Losartan: The K-Central Study

American Journal of Hypertension ◽

10.1093/ajh/hpz050 ◽

2019 ◽

Vol 32 (10) ◽

pp. 992-1002

Author(s):

Eun Joo Cho ◽

Hae Young Lee ◽

Ki Chul Sung ◽

Sungha Park ◽

Il-Suk Sohn ◽

...

Keyword(s):

Blood Pressure ◽

Wave Reflection ◽

Pulse Wave ◽

Blood Pressure Reduction ◽

Multicenter Trial ◽

Aortic Pulse Wave Velocity ◽

Fixed Dose ◽

Central Hemodynamics ◽

Velocity Pulse ◽

Double Blind

Abstract OBJECTIVE The main objective of this study was to evaluate non-inferiority of office mean systolic blood pressure (BP) reduction efficacy and superiority of 24-hour ambulatory central BP reduction efficacy between losartan combined with fixed dose amlodipine (L/A group) and dose up-titrated hydrochlorothiazide (L/H group) according to office BP. METHODS We conducted a prospective, randomized, double-blind multicenter trial in 231 patients with hypertensive (mean age = 59.2 ± 12.2 years). Patients received losartan 50 mg monotherapy for 4 weeks, followed by additional use of amlodipine 5 mg or hydrochlorothiazide 12.5 mg for 20 weeks after randomization. The patients who did not achieve the BP goal after 4 weeks’ randomization received an increased dose of 100 mg/5 mg for the L/A group and 100 mg/25 mg for L/H group, respectively. The 24-hour ambulatory central BP was measured at baseline and after 20 weeks’ treatment. RESULTS Office mean systolic BP reduction of L/A group was not inferior to L/H group after 4 weeks’ treatment (–17.6 ± 13.3 vs. –14.4 ± 12.6 mm Hg, P = 0.0863) and was not significantly different after 20 weeks’ treatment. (–15.7 ± 14.0 vs. –14.7 ± 15.1 mm Hg, P = 0.6130) The 24-hour ambulatory central systolic BP was significantly more reduced in the L/A group compared with that in the L/H group after 20 weeks’ treatment (–9.37 ± 10.67 vs. –6.28 ± 10.50 mm Hg, P = 0.0407). The 24-hour ambulatory central systolic BP at the completion of the study and its reduction magnitude were independently associated with reductions in aortic pulse wave velocity, pulse pressure, and wave reflection magnitude. CONCLUSION Office systolic BP reduction with L/A was not inferior to L/H after 4 week’s treatment. The combination of losartan and amlodipine was more favorable in 24-hour ambulatory central hemodynamics beyond BP-lowering efficacy than the combination of losartan and hydrochlorothiazide, regardless of office BP. CLINICAL TRIALS REGISTRATION NCT02294539

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Hacia el esclarecimiento del rol del anión cloruro en la hipertensión arterial: su vínculo con el daño oxidativo en el riñón

10.7775/rac.es.v89.i2.20034 ◽

2021 ◽

Vol 89 (2) ◽

pp. 98-106

Author(s):

Nicolas M. Kouyoumdzian ◽

Gabriel Kim ◽

Gabriel D. Robbesaul ◽

Paula D. Prince ◽

Ana M. Puyó ◽

...

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Systolic Blood Pressure ◽

Renal Cortex ◽

Fractional Excretion ◽

Thiobarbituric Acid ◽

Standard Diet ◽

Fractional Excretion Of Sodium ◽

Male Wistar Rats ◽

Gpx Activity

Introduction: The role of the chloride anion on the deleterious effects of excessive consumption of salt (NaCl) and whether its effects are independent each other of the presence of sodium remains to date, unknown and unclear. Objective: To demonstrate that both a chloride overload and a sodium overload in the diet produce deleterious effects, by different mechanisms, on systolic blood pressure (SBP), renal function and markers of oxidative stress in the kidney. Materials and Methods: Male Wistar rats were divided into four groups (n = 8 / group) and fed with different diets for three weeks: C: control (standard diet), and diets: NaCl: hypersodic-hyperchloric; Na: hypersodic without chloride and Cl: hyperchloric without sodium. Systolic blood pressure (SBP) and renal function were determined, and the production of thiobarbituric acid reactive species (TBARS) and the activity and expression of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes were evaluated in renal cortex tissue. Results: SBP increased (*) in the two groups fed with chloride. The fractional excretion of sodium and chloride increased (*) in the NaCl and Na groups. increased (*) in the renal cortex with the three diets. No changes were observed in the activity and expression of SOD and CAT. GPx activity increased (*) in the two groups that received chloride; (* p <0.05 vs C). Conclusion: Both sodium and chloride overload are associated with a higher oxidative state characterized by an increase in lipid peroxidation in the renal cortex. However, compared with Na group, only chloride overload is associated with higher GPx activity and hypertension without any changes in urinary chloride excretion, suggesting a higher renal pro-oxidant state in this experimental group.

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Fibroblast growth factor 23 is associated with fractional excretion of sodium in patients with chronic kidney disease

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy315 ◽

2018 ◽

Vol 34 (12) ◽

pp. 2051-2057 ◽

Cited By ~ 5

Author(s):

Hong Xu ◽

Ali Hashem ◽

Anna Witasp ◽

Rik Mencke ◽

David Goldsmith ◽

...

Keyword(s):

Blood Pressure ◽

Growth Factor ◽

Sodium Excretion ◽

Fibroblast Growth Factor 23 ◽

Fractional Excretion ◽

Urinary Sodium Excretion ◽

Fibroblast Growth ◽

Fractional Excretion Of Sodium ◽

Renal Sodium Handling ◽

Sodium Handling

Abstract Background Recent studies suggest that the phosphaturic hormone fibroblast growth factor 23 (FGF23) is involved in regulation of renal sodium excretion and blood pressure. There is evidence of both direct effects via regulation of the sodium-chloride symporter (NCC) in the distal tubule, and indirect effects through interactions with the renin–angiotensin–aldosterone system. However, clinical data on the association between FGF23 and renal sodium regulation is lacking. Herein, we investigated the associations of FGF23 with renal sodium handling and blood pressure in non-dialysis CKD patients. Methods This was a cross-sectional study encompassing 180 CKD patients Stage 1–5, undergoing renal biopsy. Plasma intact FGF23, 24-h urinary sodium excretion, fractional excretion of sodium (FENa) and blood pressure were measured at baseline. The association between FGF23 and renal sodium handling was explored by multivariate regression analysis. Results The median age was 52.8 years, 60.6% were men and the median estimated glomerular filtration rate (eGFR) was 50.6 mL/min/1.73 m2. In univariate analysis, FGF23 was positively associated with FENa (Spearman’s rho = 0.47; P < 0.001) and systolic blood pressure (rho = 0.17, P < 0.05), but not with plasma sodium, 24-h urinary sodium excretion or mean arterial blood pressure. The association between FGF23 and FENa remained significant after adjustment for potential confounders (multivariable adjusted β coefficient 0.60, P < 0.001). This association was stronger among the 107 individuals with eGFR <60 mL/min/1.73 m2 (β = 0.47, P = 0.04) and in the 73 individuals on any diuretics (β = 0.88, P < 0.001). Adjustment for measured GFR instead of eGFR did not alter the relationship. Conclusions FGF23 is independently associated with increased FENa in non-dialysis CKD patients. These data do not support the notion that FGF23 causes clinically significant sodium retention. Further studies are warranted to explore the mechanism underlying this association.

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Effects of angiotensins on day-night fluctuations and stress-induced changes in blood pressure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00583.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. R1663-R1671 ◽

Cited By ~ 37

Author(s):

Aline Nardoni Gonçalves Braga ◽

Marisa Da Silva Lemos ◽

José Roberto Da Silva ◽

Walkíria Ramos Peliky Fontes ◽

Robson Augusto Souza Dos Santos

Keyword(s):

Blood Pressure ◽

Restraint Stress ◽

Control Period ◽

Circadian Variation ◽

Cardiovascular Responses ◽

Ang Ii ◽

Brain Areas ◽

Induced Changes ◽

Infusion Period

In this study we evaluated by telemetry the effects of ANG II and ANG-(1–7) infusion on the circadian rhythms of blood pressure (BP) and heart rate (HR) and on the cardiovascular adjustment resulting from restraint stress in rats. ANG II or ANG-(1–7) or vehicle were infused subcutaneously for 7 days. Restraint stress was carried out before, during, and after infusion at 7-day intervals. Parallel with an increase in MAP, ANG II infusion produced an inversion of MAP circadian rhythm with a significant MAP acrophase inversion. It also produced bradycardia during the first 3 days of infusion. Thereafter, HR progressively increased, reaching values similar to or above those of the control period at the end of the infusion period. HR circadian variation was not changed by ANG II infusion. Strikingly, ANG II significantly attenuated the increase in MAP induced by restraint stress without altering the HR response. ANG-(1–7) infusion produced a slight but significant decrease in MAP restricted to the daytime period. No significant changes in the MAP acrophase were observed. In addition, ANG-(1–7) infusion produced a small but significant sustained bradycardia. ANG-(1–7) did not change cardiovascular responses to restraint stress. These data indicate that ANG II can influence the activity of brain areas involved in the determination of stress-induced or circadian-dependent variations of blood pressure without changing HR fluctuations. A significant modulatory influence of ANG-(1–7) on basal MAP and HR is also suggested.

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Effect of inhibition of MAO and COMT on intrarenal dopamine and serotonin and on renal function

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.1.r248 ◽

2001 ◽

Vol 280 (1) ◽

pp. R248-R254 ◽

Cited By ~ 22

Author(s):

Yongqing Wang ◽

Theresa J. Berndt ◽

Jennifer M. Gross ◽

Michael A. Peterson ◽

Mathew J. So ◽

...

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Monoamine Oxidase ◽

Filtration Rate ◽

Interstitial Fluid ◽

Fractional Excretion ◽

Urine Flow ◽

Arterial Blood ◽

Fractional Excretion Of Sodium

The purpose of the present investigation was to study the effects of inhibition of monoamine oxidase (MAO) and/or catechol- O-methyltransferase (COMT), enzymes involved in the degradation of dopamine (DA) and serotonin (5-HT), on intrarenal DA and 5-HT, as reflected in the renal interstitial fluid (RIF) microdialysate and urine, and on renal function. Inhibition of MAO selectively increased RIF 5-HT from 3.16 ± 0.38 to 8.03 ± 1.83 pg/min ( n = 7, P < 0.05), concomitant with decreases in mean arterial blood pressure and glomerular filtration rate (2.09 ± 0.18 to 1.57 ± 0.22 ml/min, n = 7, P < 0.05). Inhibition of COMT significantly increased RIF DA (3.47 ± 0.70 to 8.68 ± 1.96 pg/min, n = 9, P < 0.05), urinary DA (2.00 ± 0.16 to 2.76 ± 0.26 ng/min, n = 9, P < 0.05), and absolute excretion of sodium (6.42 ± 2.00 to 9.82 ± 1.62 μmol/min, n = 10, P < 0.05). Combined inhibition of MAO and COMT significantly increased RIF DA, urinary DA, and urinary 5-HT, which was accompanied with increases in urine flow rate, and absolute (3.03 ± 0.59 to 8.40 ± 1.61 μmol/min, n = 9, P < 0.01) and fractional excretion of sodium. We conclude that inhibition of MAO selectively increases RIF 5-HT. COMT appears to be more important than MAO in the metabolism of intrarenal DA. Physiological increases in intrarenal DA/5-HT induced by inhibition of their degrading enzymes are accompanied with significant alterations of renal function.

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Response to atrial natriuretic peptide in dogs with hypovolemic acute pancreatitis

AJP Renal Physiology ◽

10.1152/ajprenal.1989.256.2.f211 ◽

1989 ◽

Vol 256 (2) ◽

pp. F211-F217

Author(s):

M. Levy ◽

P. Cernacek

Keyword(s):

Blood Pressure ◽

Acute Pancreatitis ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Plasma Volume ◽

Sodium Excretion ◽

Fractional Excretion ◽

Fractional Excretion Of Sodium ◽

Acute Renal Insufficiency ◽

Atrial Natriuretic

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.

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A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice

Pharmaceutics ◽

10.3390/pharmaceutics14010084 ◽

2021 ◽

Vol 14 (1) ◽

pp. 84

Author(s):

Bethany L. Goodlett ◽

Chang Sun Kang ◽

Eunsoo Yoo ◽

Shobana Navaneethabalakrishnan ◽

Dakshnapriya Balasubbramanian ◽

...

Keyword(s):

Blood Pressure ◽

Immune Cells ◽

Fractional Excretion ◽

Vegf Receptor ◽

Nanoparticle Delivery ◽

Fractional Excretion Of Sodium ◽

Induced Hypertension ◽

Integral Role ◽

Factor C ◽

Endothelial Growth Factor

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice. We hypothesized that targeted nanoparticle delivery of vascular endothelial growth factor-C (VEGF-C) to the kidney would induce renal lymphangiogenesis, lowering blood pressure in hypertensive mice. A kidney-targeting nanoparticle was loaded with a VEGF receptor-3-specific form of VEGF-C and injected into mice with angiotensin II-induced hypertension or LNAME-induced hypertension every 3 days. Nanoparticle-treated mice exhibited increased renal lymphatic vessel density and width compared to hypertensive mice injected with VEGF-C alone. Nanoparticle-treated mice exhibited decreased systolic blood pressure, decreased pro-inflammatory renal immune cells, and increased urinary fractional excretion of sodium. Our findings demonstrate that pharmacologically expanding renal lymphatics decreases blood pressure and is associated with favorable alterations in renal immune cells and increased sodium excretion.

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Multicenter trial of erythropoietin in patients on peritoneal dialysis.

Journal of the American Society of Nephrology ◽

10.1681/asn.v571517 ◽

1995 ◽

Vol 5 (7) ◽

pp. 1517-1529

Author(s):

A R Nissenson ◽

S Korbet ◽

M Faber ◽

J Burkart ◽

D Gentile ◽

...

Keyword(s):

Blood Pressure ◽

Peritoneal Dialysis ◽

Maintenance Phase ◽

Multicenter Trial ◽

Hemodialysis Patients ◽

Recombinant Erythropoietin ◽

Dialysis Patients ◽

Double Blind ◽

Transfusion Requirements ◽

Wide Range

A randomized, double-blind, placebo-controlled, multicenter trial was performed to assess the safety and efficacy of subcutaneous recombinant erythropoietin (EPO) in peritoneal dialysis patients. Seventy-eight patients were randomized to receive EPO and 74 received placebo during the first 12 wk. After this, placebo patients with hematocrit less than 32% entered the EPO maintenance phase along with the initial EPO patients. Hematocrit rose significantly in the EPO group from 23.8 to 32% after 6 wk, and this was sustained at 33.7% at 12 wk. In the placebo group, the prestudy hematocrit was 23.8% as well, and no significant change in hematocrit occurred over 12 wk. Concomitant with the rise in hematocrit, transfusion requirements fell only in the EPO group. Eighty-eight percent of patients receiving EPO had their anemia ameliorated by Week 12 of the study. There was a wide range of dosage requirements during the maintenance phase, ranging from 8,000 U thrice weekly to 4,000 U every other week. Adverse events after EPO were similar to those seen in hemodialysis patients given this agent, with hypertension developing or worsening in 55% of EPO patients during the initial 12 wk of therapy. Blood pressure was more likely to rise in patients with hypertension before receiving EPO. EPO is safe and effective in peritoneal dialysis patients, as it is in hemodialysis patients. Other than a rise in blood pressure, which is manageable with antihypertensives and ultrafiltration with dialysis, no serious side effects are seen. The optimal target hematocrit, effects of anemia improvement on quality of life, and end-organ (heart, brain) effects of anemia improvement in this patient population require further study.

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Endogenous versus Exogenous Lithium Clearance for Evaluation of Dopamine-Induced Changes in Renal Tubular Function

Clinical Science ◽

10.1042/cs0900511 ◽

1996 ◽

Vol 90 (6) ◽

pp. 511-515 ◽

Cited By ~ 5

Author(s):

Niels V. Olsen ◽

Niels Fogh-Andersen ◽

Svend Strandgaard ◽

Paul P. Leyssac

Keyword(s):

Plasma Concentrations ◽

Fractional Excretion ◽

Random Order ◽

Baseline Period ◽

Tubular Function ◽

Sodium Reabsorption ◽

Lithium Clearance ◽

Double Blind ◽

Baseline Values ◽

Induced Changes

1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 μg min−1 kg−1 of dopamine. 2. Baseline values of endogenous CLi and fractional excretion of lithium (FELi) [27.0 (23.5–30.5) ml/min and 24.2 (203–28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9–35.4) ml/min (P < 0.05) and 27.4 (25.2–29.6)% (P < 0.05); lithium, 600 mg: 33.4 (29.2–37.6) ml/min (P < 0.05) and 28.6 (26.3–31.0)% (P < 0.01)]. Both test doses of lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5–46.5) ml/min (endogenous lithium, P < 0.001), 43.2 (40.8–45.6) ml/min (450 mg of lithium, P < 0.01) and 44.9 (41.3–48.4) ml/min (600 mg of lithium, P < 0.001), respectively. FELi increased to 32.2 (27.5–37.0)% (P < 0.01), 35.4 (33.0–37.7)% (P < 0.01) and 35.9 (32.8–38.9)% (P < 0.01), respectively. Values during dopamine infusion did not differ significantly. 4. The lower baseline values of endogenous CLi and FELi compared with exogenous values suggest that CLi in humans depends on the plasma concentrations of lithium. However, the effect of dopamine on CLi and FELi was expressed to the same extent with endogenous and exogenous lithium, indicating that the two methods are interchangeable for estimation of dopamine-induced changes in tubular function.

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