Background. Low 25-hydroxy-vitamin D (25(OH)D) levels are inversely related to blood pressure (BP) and have been associated with incident hypertension.

Renal denervation (RDN), treating resistant hypertension, has, in open trial design, been shown to lower blood pressure (BP) dramatically, but this was primarily with respect to office BP. We conducted a SHAM-controlled, double-blind, randomized, single-center trial to establish efficacy data based on 24-h ambulatory BP measurements (ABPM). Inclusion criteria were daytime systolic ABPM at least 145 mmHg following 1 month of stable medication and 2 weeks of compliance registration. All RDN procedures were carried out by an experienced operator using the unipolar Medtronic Flex catheter (Medtronic, Santa Rosa, California, USA). We randomized 69 patients with treatment-resistant hypertension to RDN (n = 36) or SHAM (n = 33). Groups were well balanced at baseline. Mean baseline daytime systolic ABPM was 159 ± 12 mmHg (RDN) and 159 ± 14 mmHg (SHAM). Groups had similar reductions in daytime systolic ABPM compared with baseline at 3 months [-6.2 ± 18.8 mmHg (RDN) vs. -6.0 ± 13.5 mmHg (SHAM)] and at 6 months [-6.1 ± 18.9 mmHg (RDN) vs. -4.3 ± 15.1 mmHg (SHAM)]. Mean usage of antihypertensive medication (daily defined doses) at 3 months was equal [6.8 ± 2.7 (RDN) vs. 7.0 ± 2.5 (SHAM)].RDN performed at a single center and by a high-volume operator reduced ABPM to the same level as SHAM treatment and thus confirms the result of the HTN3 trial. Further, clinical use of RDN for treatment of resistant hypertension should await positive results from double-blinded, SHAM-controlled trials with multipolar ablation catheters or novel denervation techniques.

Arginine vasopressin (AVP) mediates water transport in the renal collecting ducts by forming water channels of aquaporin-2 (AQP2) in the apical plasma membrane. AQP2 is excreted in human urine. We wanted to test the hypothesis that urinary excretion of AQP2 (u-AQP2) reflects the effect of AVP on the renal collecting ducts during water deprivation and hypertonic saline infusion in healthy subjects. Fifteen healthy subjects underwent a 24-h period of fluid restriction. Urine and blood samples were collected at timed intervals. Fifteen healthy subjects were given 7 ml/kg 3% hypertonic saline infusion for 30 min. Urine and blood samples were collected at timed intervals. During fluid restriction, the u-AQP2 rate increased from 3.9 (25th percentile: 3.1; 75th percentile: 5.2) to 7.6 (5.9–9.1; P < 0.001) ng/min, and the plasma AVP (p-AVP) level increased from 0.5 (0.4–0.6) to 3 (1.7–3.3) pmol/l. There was a positive correlation between the maximum change in u-AQP2 rate and the maximum change in p-AVP (r = 0.57,P < 0.03). During the infusion study, u-AQP2 rate was at maximum 90 min after the infusion [baseline: 4.5 ng/min (3.5–4.8); 90 min: 5 ng/min (4.5–6.0) P < 0.02]. p-AVP increased from 1.0 (0.9–1.1) to 1.5 (1.2–1.8;P < 0.002) pmol/l. There was a positive correlation between the maximum change in u-AQP2 rate and the maximum change in p-AVP (r = 0.83; P < 0.0001). It can be concluded that p-AVP and u-AQP2 are increased during thirst and hypertonic saline infusion and that u-AQP2 reflects the action of AVP on the collecting ducts.

Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (−18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (−36%, P < 0.005; −65%, P < 0.05; −90%, P < 0.005; and −13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.

Patients on chronic dialysis are at increased risk of vitamin D deficiency. In observational studies plasma 25-hydroxyvitamin D (p-25(OH) D) levels are inversely correlated with plasma BNP and adverse cardiovascular outcomes. Whether a causal relation exists has yet to be established. The aim of this study was to test the hypothesis that cholecalciferol supplementation improves cardiac function and reduces blood pressure (BP) and pulse wave velocity (PWV) in patients on chronic dialysis.

The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FE_Na), free water clearance (C_H2O), urinary excretion of PGE₂(u-PGE₂) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE₂were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism.