The role of renal proximal tubule transport in the regulation of blood pressure

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT(1A) receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.

Korean Version of the Overactive Bladder Symptom Score Questionnaire: Translation and Linguistic Validation / 대한배뇨장애요실금학회지

PURPOSE: The overactive bladder symptom score (OABSS) consists of 4 questions regarding OAB symptoms. The aim of this study was to develop Korean version of the OABSS from the original Japanese version, with subsequent linguistic validation. METHODS: Between February and May 2008, the translation and linguistic validation process was performed as follows: a forward translation, reconciliation, backward translation, cognitive debriefing, and final proofreading. RESULTS: A forward translation from the original version of the OABSS to the Korean language was carried out by 2 native Korean speakers, who were also fluent in Japanese. Reconciliation was made after review of both translations by a panel consisting of both translators and one of the authors. Another bilingual translator who had never seen the original version of the OABSS carried out a translation of the reconciled version back into Japanese, and the original and backward-translated versions were subsequently compared. After discussion of all discrepancies between both versions by the panel, a second Korean version was produced. During cognitive debriefing, 5 outpatients with OAB reported that each question of the Korean version was significant and appropriate for their symptoms. However, 2 patients said that some parts of the questions or instructions were not clear or were not easy to understand. According to the cognitive debriefing, some words and phrases were revised into more understandable expressions. CONCLUSIONS: A Korean version of the OABSS was developed and linguistic validation was performed. Further studies are needed to assess the reproducibility and validity of the questionnaire in Korean populations.

Beta3-Adrenoceptor Agonists: Possible Role in the Treatment of Overactive Bladder

In the present review article, we present an overview of beta-adrenoceptor (beta-AR) subtype expression at the mRNA and receptor protein levels in the human detrusor, the in vitro and in vivo bladder function of the beta3-AR, the in vivo effect of beta3-AR agonists on detrusor overactivity in animal models, and the available results of clinical trials of beta3-AR agonists for treating overactive bladder (OAB). There is a predominant expression of beta3-AR mRNA in human bladder, constituting 97% of total beta-AR mRNA. Also, functionally, the relaxant response of human detrusor to catecholamines is mainly mediated through the beta3-ARs. Moreover, the presence of beta1-, beta2-, and beta3-AR mRNAs in the urothelium and suburothelial layer of human bladder has been identified. Stimulation of urothelial beta-ARs results in the release of nitric oxide and an unknown substance inhibiting detrusor contractions from the urothelium. Intravenous application of CL316,243, a selective beta3-AR agonist, in rats selectively inhibits mechano-sensitive Adelta-fiber activity of the primary bladder afferents. A number of selective beta3-AR agonists are currently being evaluated in clinical trials for OAB with promising preliminary results. In conclusion, the beta3-AR agonists are the most notable alternative class of agents to antimuscarinics in the pharmacological treatment of OAB. The beta3-AR agonists act to facilitate bladder storage function probably through at least two mechanisms: first, direct inhibition of the detrusor, and second, inhibition of bladder afferent neurotransduction.