Objective: Recent trials confirmed the lowering effect of renal denervation (RDN) on blood pressure (BP). We aimed to analyze the impact of RDN on BP variability and circadian rhythm. Design and method: Out of 31 truly resistant patients whose secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18 (10 m, 8 w, average age 49.3) were eligible for analyses. Office BP, ABPM, central BP, and PWV were measured with Omron M6, Mobilograph, and Sphygmocor devices. Sympathetic/parasympathetic activity was measured with ANX-3.0 ANSAR device. All RDN procedures (Spyral Medtronic) were done by one physician (average number of ablation spots was 41/procedure). Patients were examined the day before and that day, 1,3,6, and 12 months after the RDN. The response was a drop of office systolic BP by 10 mmHg or more 6 months after RDN. There were no differences in the RDN procedure between responders and non-responders. Results: Office and ABPM values dropped the day after RDN and remained significantly lower at the end of the follow-up (6.5/-5.5 and -16.2/9 mmHg, respectively). We failed to find changes in BP variability (SD) after RDN. However, a significant decrease in morning BP surge was observed immediately the day after RDN (-12.4) and was even lower at the end of the follow-up (-18.8 mmHg). Substantial number of patients who had an abnormal nocturnal BP pattern became dippers. Central systolic BP and PWV decreased (-6.3 mmHg and -0.72 m/s, respectively). LFa/RFa decreased the day after RDN and reminded lower during the follow-up period. After RDN morning BP surge remained stable and normal in responders; however, in non-responders, it decreased immediately after RDN (-21.2) and remained lower during the follow-up till the last visit (-33.3). Conclusions: Significant improvements in circadian rhythm and several parameters of central hemodynamics were observed after RDN indicating that RDN might be considered as a pathway to the complete, so-called perfect 24-hour BP control. Observed beneficial effects run in parallel with the observed decrease in sympathetic activity. Importantly, even in non-responders, RDN had a beneficial effect on morning BP surge.
INTRODUCTION. Sodium-independent sulfate anion transporter (sat-1 ; Slc26a1) plays a major role in transport of oxalate (OX) across the cell membrane by exchanging OX for sulfate or bicarbonate. Sat-1 mRNA has been detected strongly in liver and kidney and weakly in few other organs in rats, mice, and humans. By immunocytochemistry (IC), the protein has been localized in rats to the sinusoidal membrane of hepatocytes and basolateral membrane of proximal tubules (PT) in the kidney cortex, with the male (M)-dominant expression. In liver, which is a major OX producer, sat-1 mediates the extrusion of OX and uptake of sulfate, whereas in PT, it mediates the OX uptake, mainly in exchange for intracellular sulfate. In middle-aged humans, OX is a major cause of sex-related urolithiasis ; men excrete more OX and have higher incidence of OX stones then women. Accordingly, in studies of experimental urolithiasis in ethylene glycol (EG)-treated rats, testosterone stimulated, whereas female (F) sex hormones inhibited the urine excretion of OX and formation of OX stones. The role of OX transporters that in liver and kidneys exhibit the sex-related expression, such as sat-1, in the development of OX urolithiasis is not known. In the present study, we tested the expression of sat-1 at the protein and mRNA levels in the liver and kidneys of EG-treated rats. METHODS. Adult M and female (F) Wistar strain rats were treated with EG (0, 75% v/v in drinking water) for one month. Controls drunk water without EG. 24-h urine was collected in metabolic cages a day before sacrificing. OX in the blood plasma and urine were determined by ion-chromatography. Tissue morphology and OX crystals in the urine sediment were checked by light microscopy. Sat-1 protein expression was studied using a polyclonal antibody by IC in p-formaldehyde-fixed tissue cryosections, and by Western blotting of total cell membranes isolated from tissue homogenates. Tissue expression of sat-1 mRNA was studied by real time RT-PCR. RESULTS. In control M and F animals, the M-dominant sex differences in the urine excretion of OX, in the number and size of urine OX crystals, and in the expression of sat-1 protein (but not mRNA) in liver and kidneys, were confirmed. Compared to controls, the EG-treated animals exhibited: a) in plasma, 100% (F) and 4-fold (M) higher concentration of OX, b) in urine, 100% (F) and 17-fold (M) higher OX excretion, c) in urine sediment, similar and low abundance of small OX crystals in F, and increased abundance of large OX crystals in M, d) in tissues of both sexes, un-affected morphology in liver, and dilatated PT and distended peritubular spaces in kidneys, e) upregulated expression of sat-1 protein in the F liver and kidneys to the level in M organs, f) unchanged expression of sat-1 protein in the M liver and kidneys, and g) unchanged expression of sat-1 mRNA in both organs of F and M animals. CONCLUSION. Whereas the blood and urinary parameters in EG-treated rats indicate the low and high oxaluric state in F and M rats, respectively, the EG-induced elevated expression of sat-1 protein in the F liver and kidneys, and unchanged expression of this protein in M organs, indicate that sat-1 plays no significant role in generation of OX urolithiasis in EG-treated animals.
U knjizi je prikazana klinicka kemija i molekularna dijagnostika te najnovija dostignuca laboratorijske medicine i rezultati u tim podrucjima postignuti u Hrvatskoj te rezultati dobivene kroz međunarodnu suradnju (dislipidemije i analiza ekspresije gena pomocu mikropostroja).
Abstract Chloride/formate exchanger (CFEX; SLC26A6) mediates oxalate transport in various mammalian organs. Studies in Cfex knockout mice indicated its possible role in development of male-dominant hyperoxaluria and oxalate urolithiasis. Rats provide an important model for studying this pathophysiological condition, but data on Cfex (rCfex) localisation and regulation in their organs are limited. Here we applied the RT-PCR and immunochemical methods to investigate rCfex mRNA and protein expression and regulation by sex hormones in the pancreas, small intestine, liver, and kidneys from intact prepubertal and adult as well as gonadectomised adult rats treated with sex hormones. rCfex cDNA-transfected HEK293 cells were used to confirm the specificity of the commercial anti-CFEX antibody. Various biochemical parameters were measured in 24-h urine collected in metabolic cages. rCfex mRNA and related protein expression varied in all tested organs. Sex-independent expression of the rCfex protein was detected in pancreatic intercalated ducts (apical domain), small intestinal enterocytes (brush-border membrane; duodenum > jejunum > ileum), and hepatocytes (canalicular membrane). In kidneys, the rCfex protein was immunolocalised to the proximal tubule brush-border with segment-specific pattern (S1=S2<S3), and both rCfex mRNA and protein expression exhibited male-dominant sex differences driven by stimulatory effects of androgens after puberty. However, urinary oxalate excretion was unrelated to renal rCfex protein expression. While the effect of male-dominant expression of rCfex in renal proximal tubules on urine oxalate excretion remains unknown, its expression in the hepatocyte canalicular membrane may be a pathway of oxalate elimination via bile.