The effect of vitamin D3 supplementation on markers of cardiovascular health in hyperparathyroid, vitamin D insufficient women: a randomized placebo-controlled trial.

PURPOSE: Emerging data supports an association between parathyroid hormone (PTH) and aldosterone. It has been speculated, that potential adverse cardiovascular effects of vitamin D insufficiency may partly be caused by the development of secondary hyperparathyroidism with increased activity of the renin-angiotensin-aldosterone system (RAAS). We aimed to investigate the effect of normalizing vitamin D status and/or reducing PTH levels on RAAS activity and other markers of cardiovascular health. METHODS: In a double-blinded study during wintertime, we randomized 81 healthy postmenopausal women with secondary hyperparathyroidism (PTH > 6.9 pmol/l) and 25-hydroxy-vitamin D (25(OH)D) levels < 50 nmol/l to 12 weeks of treatment with vitamin D3 70 µg/day (2800 IU/day) or identical placebo. Markers of cardiovascular health were defined as changes in the plasma RAAS, glycated hemoglobin, lipids, and lipoproteins, blood pressure, vascular stiffness, heart rate, and cardiac conductivity. RESULTS: Compared to placebo, vitamin D3 treatment significantly increased plasma levels of 25(OH)D and 1,25(OH)2D by 230% (95% CI: 189-272%) and 58% (190-271%), respectively. Vitamin D3 treatment reduced PTH by 17% (11-23%), but did not reduce RAAS activity. Compared to placebo, vitamin D3 treatment increased plasma levels of high-density lipoproteins (HDL) by 4.6% (0.12-9.12%), but did not affect other measured indices. CONCLUSIONS: Vitamin D3 supplementation normalized vitamin D levels and reduced PTH. The supplement increased levels of HDL, but had no effects on RAAS activity or other indices of cardiovascular health.

The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial).

OBJECTIVES: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. METHODS: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. RESULTS: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. CONCLUSIONS: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Effect of tolvaptan on renal handling of water and sodium, GFR and central hemodynamics in autosomal dominant polycystic kidney disease during inhibition of the nitric oxide system: a randomized, placebo-controlled, double blind, crossover study.

BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis. Nitric oxide (NO) stimulates natriuresis and diuresis, but its role is unknown during tolvaptan treatment in ADPKD. METHODS: Eighteen patients with ADPKD received tolvaptan 60 mg or placebo in a randomized, placebo-controlled, double blind, crossover study. L-NMMA (L-NG-monomethyl-arginine) was given as a bolus followed by continuous infusion during 60 min. We measured: GFR, urine output (UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensinII (p-AngII), aldosterone (p-Aldo), and central blood pressure (cBP). RESULTS: During tolvaptan with NO-inhibition, a more pronounced decrease was measured in UO, CH2O (61% vs 43%) and FENa (46% vs 41%) after placebo than after tolvaptan; GFR and u-AQP2 decreased to the same extent; p-AVP increased three fold, whereas u-ENaCγ, PRC, p-AngII, and p-Aldo remained unchanged. After NO-inhibition, GFR increased after placebo and remained unchanged after tolvaptan (5% vs -6%). Central diastolic BP (CDBP) increased to a higher level after placebo than tolvaptan. Body weight fell during tolvaptan treatment. CONCLUSIONS: During NO inhibition, tolvaptan antagonized both the antidiuretic and the antinatriuretic effect of L-NMMA, partly via an AVP-dependent mechanism. U-AQP2 was not changed by tolvaptan, presumeably due to a counteracting effect of elevated p-AVP. The reduced GFR during tolvaptan most likely is caused by the reduction in extracellular fluid volume and blood pressure. TRIAL REGISTRATION: Clinical Trial no: NCT02527863 . Registered 18 February 2015.

Effect of sodium nitrite on renal function and sodium and water excretion and brachial and central blood pressure in healthy subjects: a dose-response study.

Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2 on hemodynamics, sodium excretion, and glomerular filtration rate (GFR). In a single-blinded, placebo-controlled, crossover study, we infused placebo (0.9% NaCl) or 0.58, 1.74, or 3.48 µmol NaNO2·kg-1·h-1 for 2 h in 12 healthy subjects, after 4 days of a standard diet. Subjects were supine and water loaded. We measured brachial and central blood pressure (BP), plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma nitrite (P-[Formula: see text]), GFR by Cr-EDTA clearance, fractional excretion of sodium (FENa) free water clearance (CH2O), and urinary excretion rate of guanosine 3',5'-cyclic monophosphate (U-cGMP). The highest dose reduced brachial systolic BP (5.6 mmHg, P = 0.003), central systolic BP (5.6 mmHg, P = 0.035), and CH2O (maximum change from 3.79 to 1.27 ml/min, P = 0.031) and increased P-[Formula: see text] (from 0.065 to 0.766 µmol/l, P < 0.001), while reducing U-cGMP (from 444 to 247 pmol/min, P = 0.004). GFR, FENa, P-AVP, and the components in the renin-angiotensin-aldosterone system did not change significantly. In conclusion, intravenous NaNO2 induced a dose-dependent reduction of brachial and central BP. The hemodynamic effect was not mediated by the renin-angiotensin-aldosterone system. NaNO2 infusion resulted in a vasopressin-independent decrease in CH2O and urine output but no change in urinary sodium excretion or GFR. The lack of increase in cGMP accompanying the increase in [Formula: see text] suggests a direct effect of nitrite or nitrate on the renal tubules and vascular bed with little or no systemic conversion to NO.

Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects.

BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron's principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium and systemic hemodynamics, during baseline and NO-inhibition with L-NMMA (L-NG-monomethyl-arginine). METHODS: In a randomized, placebo-controlled, double blind, cross over study, 15 healthy subjects received tolvaptan 15, 30 and 45 mg or placebo. L-NMMA was given as a bolus followed by continuous infusion during 60 min. We measured urine output (UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma vasopressin (p-AVP) and central blood pressure (cBP). RESULTS: During baseline, FENa was unchanged. Tolvaptan decreased u-ENaCγ dose-dependently and increased p-AVP threefold, whereas u-AQP2 was unchanged. During tolvaptan with NO-inhibition, UO and CH2O decreased dose-dependently. FENa decreased dose-independently and u-ENaCγ remained unchanged. Central BP increased equally after all treatments. CONCLUSIONS: During baseline, fractional excretion of sodium was unchanged. During tolvaptan with NO-inhibition, renal water excretion was reduced dose dependently, and renal sodium excretion was reduced unrelated to the dose, partly via an AVP dependent mechanism. Thus, tolvaptan antagonized the reduction in renal water and sodium excretion during NO-inhibition. Most likely, the lack of decrease in AQP2 excretion by tolvaptan could be attributed to a counteracting effect of the high level of p-AVP. TRIAL REGISTRATION: Clinical Trial no: NCT02078973 . Registered 1 March 2014.

The cardiovascular system in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene.

OBJECTIVE: Loss-of-function variants in the gene encoding the calcium-sensing receptor (CASR) result in familial hypocalciuric hypercalcemia (FHH), causing hypercalcemia with high normal or elevated parathyroid hormone levels. The CASR may also influence electrolyte and water homeostasis. It is unknown whether FHH affects cardiovascular health. We, therefore investigated whether FHH is associated with changes in the regulation of the cardiovascular system by measuring 24-h blood pressure (BP), arterial stiffness and vasoactive hormones. DESIGN: Cross-sectional study comparing 50 patients with FHH to age- and gender-matched controls. RESULTS: Studied subjects (69% women) had a mean age of 56years. A similar number of patients and controls (33%) were on treatment with antihypertensive drugs. Overall, no differences were found between groups in 24-h ambulatory BP or pulse wave velocity. However, compared with controls, diastolic BP during nighttime was lower in FHH females (60±5 vs 66±9mmHg, P<0.01) and higher in FHH males (69±6 vs 64±5mmHg, P=0.02). FHH was associated with a significantly higher plasma osmolality (P<0.01), higher plasma levels of vasopressin (P<0.01) and a higher renal excretion of epithelial sodium channels (ENaCs) (P=0.03), whereas urine aquaporin-2 and plasma sodium, aldosterone and renin did not differ between groups. FHH patients had a lower urinary volume with an increased osmolality if analyses were restricted to those not on treatments with antihypertensive drugs. CONCLUSIONS: FHH does not seem to be associated with an increased risk of CVD.

High Prevalence of Hypertension in a Danish Population Telemedical Home Measurement of Blood Pressure in Citizens Aged 55-64 Years in Holstebro County.

BACKGROUND: Home blood pressure (HBP) is prognostically superior to office BP (OBP) and similar to ambulatory BP measurements. We determined the prevalence of hypertension using HBP with telemedical data transmission in the municipality of Holstebro, Denmark (57,000 citizens). METHODS: Using the Civil Registration System, we invited citizens aged 55-64 years to have their OBP and HBP measured using telemedical data transmission. Elevated OBP was defined as ≥140/90mm Hg. HBP was measured 3 times daily on 3 consecutive days with 3 measurements on each occasion. HBP was the mean of all measurements on day 1 and 3, and hypertension was defined as ≥135/85mm Hg. RESULTS: We included 3,102 citizens who had performed at least 12 HBP measurements during day 2 and 3. Group 1: (n = 1,464, 47%) had both normal OBP and HBP. Group 2: (n = 838, 27%) had both elevated OBP and HBP indicating persistent hypertension. Group 3: (n = 560, 18%) had elevated OBP and normal HBP indicating white coat hypertension (WCH). Group 4: (n = 240, 8%) had normal OBP and elevated HBP indicating masked hypertension (MH). Thus, 1,078 (35%, groups 2 and 4) were untreated or insufficiently treated. Awareness of hypertension was registered in 950 patients (31%) and of these 49% had a normal HBP. CONCLUSIONS: This is the first large-scale study to eliminate completely reporting bias by using telemedical transmission of BP data. One third of citizens in the age group 55-64 years had an abnormally high HBP, and one fourth either had WCH or MH. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identification number: NCT02355392.

[Acute oliguric renal failure and haemolytic anaemia following infectious mononucleosis]. / Akut nyresvigt og hæmolytisk anæmiefter infektiøs mononukleose.

A 19-year-old man was admitted to hospital due to fatigue, nausea, abdominal pain and faint. He was pale and icteric, awake with sufficient respiration and circulation. He had infectious mononucleosis complicated with acute oliguric renal failure and severe haemolytic anaemia with a positive Coombs test. He had a cold agglutinin syndrome. The treatment comprised intermittent haemodialysis, plasmapheresis and heating. He recovered completely after two months.

Urinary aquaporin-2 excretion before and after transjugular intrahepatic portosystemic shunt insertion for refractory ascites.

OBJECTIVE: The role of renal aquaporin-2 (AQP2) water channel turnover in patients with liver cirrhosis, portal hypertension and water retention remains unclear. Transjugular intrahepatic portosystemic shunt (TIPS) insertion reduces portal hypertension, improves water excretion and lowers plasma vasopressin. The aim of this study was to establish whether TIPS insertion decreases urinary AQP2 excretion (uAQP2) in parallel with improved water excretion. MATERIAL AND METHODS: Fourteen cirrhosis patients with refractory ascites were studied before TIPS insertion and 4 and 12 weeks after insertion. A 24-h urine collection was followed by an oral water load (20 ml/kg body weight) with a 4-h blood and urine sampling. RESULTS: TIPS reduced the portal pressure gradient from a median 18(4) (25-75% InterQuartile-range) to 7(2) mmHg, p < 0.05 and the need for diuretics (p < 0.05). TIPS increased plasma sodium from 136(6) mmol/l to 139(4), (p < 0.05) and diuresis from 1650(1043) ml/24 h to 2230(560) (p < 0.05), although the 24-h urinary sodium excretion did not change. There was no change in the baseline uAQP2 before 274(249) ng/(mmol creatinine/24 h) and 12 weeks after TIPS 242(201). There were no systematic changes in uAQP2, plasma vasopressin or other vasoactive substances during the water loads, before or after TIPS. CONCLUSION: The effective amelioration of portal hypertension improved the patient's water excretion and plasma sodium, but there was no change in renal AQP2 trafficking or vasopressin. These findings do not support a primary role for renal AQP2 water channels in portal hypertensive water retention.

The effect of 6% hydroxyethyl starch 130/0.4 on renal function, arterial blood pressure, and vasoactive hormones during radical prostatectomy: a randomized controlled trial.

BACKGROUND: Although hydroxyethyl starch (HES) is commonly used as an intravascular volume expander in surgical patients, recent studies suggest that it may increase the risk of renal failure in critically ill patients. We hypothesized that patients undergoing radical prostatectomy and receiving HES would be more likely to develop markers of renal failure, such as increasing urinary neutrophil gelatinase-associated lipocalin (u-NGAL), creatinine clearance (C(crea)), and decreasing urine output (UO). METHODS: In a randomized, double-blinded, placebo-controlled study, 40 patients referred for radical prostatectomy received either 6% HES 130/0.4 or saline 0.9%; 7.5 mL/kg during the first hour of surgery and 5 mL/kg in the following hours; u-NGAL, urine albumin, C(crea), UO, arterial blood pressure, and plasma concentrations of creatinine, renin, angiotensin II, aldosterone, and vasopressin were measured before, during, and after surgery. RESULTS: Thirty-six patients completed the study. u-NGAL, C(crea), UO, plasma neutrophil gelatinase-associated lipocalin, p-creatinine, urine albumin, and arterial blood pressure were the same in both groups. Blood loss was higher in the HES group (HES 1250 vs saline 750 mL), while p-albumin was reduced to a significantly lower level. P-renin and p-angiotensin-II increased in both groups, whereas p-aldosterone and p-vasopressin increased significantly in the saline group. CONCLUSIONS: We found no evidence of nephrotoxicity after infusion of 6% HES 130/0.4 in patients undergoing prostatectomy with normal preoperative renal function. Hemodynamic stability and infused fluid volume were the same in both groups. We observed an increased blood loss in the group given 6% HES 130/0.4.

[High doses of aldosterone antagonist is a condition of sufficient blood pressure control in bilateral adrenal hyperplasia]. / Høj dosis af aldosteronantagonist er nødvendig for god blodtrykskontrol ved bilateral adrenal hyperplasi.

Primary aldosteronism occurs in 1-10% of hypertensive patients and is classified in adenomas or bilateral adrenal hyperplasia. Computed tomography (CT) or magnetic resonance imaging can be used to discriminate these subtypes and in guiding treatment selection. This case report describes a 65-year-old man with hypertension and hypokalaemia during 25 years. Bilateral adrenal hyperplasia was diagnosed based on a CT, and an oral sodium-loading test with measurement of renin and aldosterone confirmed the diagnosis. Blood pressure and potassium in plasma was normalized during treatment with the mineralocorticoid receptor antagonist eplerenon.

[Lithium can be given to patients on haemodialysis treatment]. / Lithium kan anvendes til patienter i hæmodialyse.

Lithium-induced nephropathy is a known complication of lithium treatment in bipolar disorder. Treatment with lithium should be discontinued, if there is evidence of lithium-induced nephropathy. However, lithium can be given to patients with end-stage-renal-disease on haemodialysis treatment, if there is no other way to control the bipolar disorder. We report one patient who was successfully treated with lithium in parallel with haemodialysis.

Associations of objectively measured physical activity and abdominal fat distribution.

INTRODUCTION/PURPOSE: Visceral adipose tissue (VAT) and physical activity are both independent predictors of Type 2 diabetes. Physical activity and overall obesity are inversely associated with each other. Yet the nature of the association between objectively measured dimensions of physical activity and abdominal fat distribution has not been well characterized. We aimed to do so in a middle-age to elderly population at high risk of diabetes. METHODS: A cross-sectional analysis of 1134 participants of the ADDITION-PRO study. VAT and subcutaneous adipose tissue (SAT) were assessed one-dimensionally by ultrasonography and physical activity with combined accelerometry and HR monitoring. Linear regression of physical activity energy expenditure (PAEE) and time spent in different physical activity intensity levels on VAT and SAT was performed. RESULTS: Median body mass index (BMI) was 26.6 kg·m and PAEE was 28.1 kJ·kg·d, with 18.9 h·d spent sedentary, 4.5 h·d in light-intensity physical activity, and 0.4 h·d in moderate-intensity physical activity. PAEE was significantly negatively associated with VAT, and in women, PAEE was also significantly negatively associated with SAT. The difference in VAT was -1.1 mm (95% confidence interval [CI] = -1.8 to -0.3) per 10-kJ·kg·d increment, and the corresponding difference in SAT for women was -0.6 mm (95% CI = -1.2 to -0.04) in models adjusted for age, sex, and waist circumference. Exchanging 1 h of light physical activity with moderate physical activity was significantly associated with VAT (-4.5 mm, 95% CI = -7.6 to -1.5). Exchanging one sedentary hour with light physical activity was significantly associated with both VAT (-0.9 mm, 95% CI = -0.1 to -1.8) and SAT (-0.4 mm, 95% CI = -0.0 to -0.7). CONCLUSIONS: In this population with low physical activity levels, cross-sectional findings indicate that increasing overall physical activity and decreasing time spent sedentary is important to avoid the accumulation of metabolically deleterious VAT.

Lack of nephrotoxicity by 6% hydroxyethyl starch 130/0.4 during hip arthroplasty: a randomized controlled trial.

BACKGROUND: Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The authors hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary excretion of neutrophil gelatinase-associated lipocalin (u-NGAL) in patients with normal renal function during hip arthroplasty. METHODS: In this randomized, double-blinded, placebo-controlled study, 40 patients referred for hip arthroplasty received either 6% HES 130/0.4 or isotonic saline 0.9%; 7.5 ml/kg during the first hour of surgery and 5 ml/kg during the following hours; 38 patients completed the study. U-NGAL, urine albumin, blood pressure, and plasma concentrations of creatinine, renin, NGAL, albumin, angiotensin-II, and aldosterone were measured before, during, and after surgery. U-NGAL was defined as primary outcome. RESULTS: There were no significant differences in U-NGAL (mean difference and 95% CI), plasma creatinine, and urine albumin during the study. U-NGAL and urine albumin increased significantly in both groups the morning after surgery but was normalized at follow-up after 10 to 12 days. Mean arterial pressure was significantly higher during the recovery period in the HES group compared with that in the control group (91 [13] and 83 [6] mmHg, mean [SD], P < 0.03). Plasma renin and angiotensin-II were nonsignificantly different in both groups, whereas plasma aldosterone was significantly lower in the HES group. Plasma albumin was reduced in both groups, but to a significantly lower level in the HES group. CONCLUSION: The study showed no evidence of a harmful effect of intraoperative infusion of 6% HES 130/0.4 on renal function in patients during hip arthroplasty.

Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects.

BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water excretion. We wanted to test the hypotheses that tolvaptan changes both renal handling of water and sodium and systemic hemodynamics during basal conditions and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA). METHODS: Nineteen healthy subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study of two examination days. Tolvaptan 15 mg or placebo was given in the morning. L-NMMA was given as a bolus followed by continuous infusion during 60 minutes. We measured urine output(UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma vasopressin (p-AVP), central and brachial blood pressure(cBP, bBP). RESULTS: During baseline conditions, tolvaptan caused a significant increase in UO, CH2O and p-AVP, and FENa was unchanged. During L-NMMA infusion, UO and CH2O decreased more pronounced after tolvaptan than after placebo (-54 vs.-42% and -34 vs.-9% respectively). U-AQP2 decreased during both treatments, whereas u-ENaCγ decreased after placebo and increased after tolvaptan. CBP and bBP were unchanged. CONCLUSION: During baseline conditions, tolvaptan increased renal water excretion. During NO-inhibition, the more pronounced reduction in renal water excretion after tolvaptan indicates that NO promotes water excretion in the principal cells, at least partly, via an AVP-dependent mechanism. The lack of decrease in u-AQP2 by tolvaptan could be explained by a counteracting effect of increased plasma vasopressin. The antagonizing effect of NO-inhibition on u-ENaC suggests that NO interferes with the transport via ENaC by an AVP-dependent mechanism.

Effects of atorvastatin on systemic and renal NO dependency in patients with non-diabetic stage II-III chronic kidney disease.

AIMS: Clinical trials suggest that statins have beneficial effects on the cardiovascular system independent from their cholesterol lowering properties. In patients with chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-N(G) -monomethyl arginine (L-NMMA) as an inhibitor of NO production. METHODS: In a randomized, placebo-controlled, crossover study patients were treated with atorvastatin for 5 days with standardized diet and fluid intake. Glomerular filtration reate (GFR), fractional excretions of sodium (FENa ), urinary excretion of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ ), vasoactive hormones (renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide) and central blood pressure (BP) estimated by applanation tonometry were measured before and after systemic administration of the NO inhibitor L-NMMA. RESULTS: Atorvastatin caused a significant reduction in U-ENaCγ , but sodium excretion, C H 2 O , FENa and u-AQP2 were not changed by atorvastatin. L-NMMA reduced renal effect variables, including GFR, FENa and u-ENaCγ and increased brachial BP and central BP to a similar extent during both treatments. Vasoactive hormones were changed in the same way by L-NMMA during atorvastatin and placebo treatment. CONCLUSION: During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, the data do not support that atorvastatin changes nitric oxide availability in patients with mild nephropathy. The reduced u-ENaC may reflect changes in sodium absorption in the nephron induced by atorvastatin.

Effects of atorvastatin on systemic and renal nitric oxide in healthy man.

Statin treatment improves endothelial function but the effects of statins on renal nitric oxide have not been clarified. In this crossover study, 26 healthy subjects received atorvastatin 80 mg per day or placebo for 5 days. After 5 days of treatment, L-N(G)-monomethyl arginine caused a similar increase in blood pressure and decrease in urine output and glomerular filtration rate. The decrease in fractional excretion of sodium to L-N(G)-monomethyl arginine was more pronounced after atorvastatin treatment. Atorvastatin did not change the response to several vasoactive hormones. The results indicate that atorvastatin increase renal nitric oxide, which may explain a part of the pleiotropic effects of statins.

Catheter-based renal denervation for treatment of resistant hypertension.

INTRODUCTION: Activation of renal sympathetic nerves is associated with the development of hypertension. Catheter-based renal sympathetic denervation with radiofrequency energy ablation is a new promising treatment option for resistant hypertension. We here report the first Danish experiences and results with this technique. MATERIAL AND METHODS: Nine patients with resistant hypertension and a day-time 24-hour ambulatory blood pressure (BP) of 152/89 mmHg ± 10/10 (standard deviation) mmHg despite treatment with 5.4 ± 1.4 anti-hypertensive drugs underwent catheter-based renal sympathetic denervation with the Symplicity catheter. RESULTS: No periprocedural complications or adverse events during follow-up were observed. Seven patients received complete ablation and two patients only partial ablation. Five patients responded to the treatment with a reduction in day-time 24-hour ambulatory BP from 158/94 ± 13/9 mmHg to 139/82 ± 10/8 mmHg (p < 0.05) at the one month follow-up and a reduction in the number of anti-hypertensive drugs from 5.4 ± 1.6 to 3.4 ± 0.9 (p < 0.05). BP in the remaining four patients was not significantly changed and antihypertensive therapy was not changed. CONCLUSION: Catheter-based renal sympathetic denervation is a feasible and in several cases also effective treatment option for patients with resistant hypertension. Adequately designed controlled trials are needed to assess the long-term safety and the full potential of this treatment.

Effect of amiloride and spironolactone on renal tubular function, ambulatory blood pressure, and pulse wave velocity in healthy participants in a double-blinded, randomized, placebo-controlled, crossover trial.

We wanted to test the hypothesis that treatment with amiloride or spironolactone reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular transport via ENaCγ and AQP2 was increased after furosemide treatment. During baseline conditions, there were no differences in ABP, CBP, renal tubular function, or plasma concentrations of vasoactive hormones. After furosemide treatment, an increase in CBP, CH(2)o, FE(Na), FE(K), u-AQP2/min, u-ENaCγ/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and sodium absorption via AQP2 and ENaC after furosemide treatment most likely are compensatory phenomena to antagonize water and sodium depletion.