Abstract 486: Uric Acid, Indoxyl Sulfate And Methylguanidine Activate The Bulbospinal Neurons In The Rostral Ventrolateral Medulla Through Their Specific Transporters
Chronic renal failure (CRF) is often accompanied with hypertension. However, the mechanism of hypertension in patients with CRF is not well known except the excess of body fluid. We considered that the mechanisms of hypertension in patients with CRF were due to increased activity of bulbospinal rostral ventrolateral medulla (RVLM) neurons caused by the stimulation of uremic toxins. The harmful effects of uremic toxins on the neurons of the bulbospinal RVLM have been scarcely examined until date. The aim of this study was to examine the effects of uremic toxins on the bulbospinal RVLM neurons electrophysiologically and histologically. To directly investigate whether RVLM neurons show sensitivity to uric acid (UA), indoxyl sulfate (IS), and methylguanidine (MG), we examined changes in the membrane potentials (MPs) of the bulbospinal RVLM neurons using the whole-cell patch-clamp technique, during superfusion of these toxins. During UA superfusion (0.05-1 mM), 29 of 33 RVLM neurons were depolarized, and during IS superfusion (0.01-5 mM), 14 of 14 RVLM neurons were depolarized. During MG superfusion (0.01-5 mM), 18 of 19 RVLM neurons were depolarized. To examine the transporters on RVLM neurons for these toxins, histological examinations were performed. As the results, all of 4 UA-depolarized RVLM neurons showed the presence of URAT 1. All of 3 IS-depolarized and four of 4 IS-depolarized RVLM neurons showed the presence of organic anion transporter (OAT) 1 and OAT 3, respectively. All of 3 MG-depolarized RVLM neurons showed the presence of organic cation transporter (OCT) 3. Our findings suggest that uremic toxins such as UA, IS, and MG increase the blood pressure by increasing the activity of the bulbospinal RVLM neurons through their specific transporters on these neurons.
Author Disclosures: N. Oshima: None. H. Onimaru: None. T. Uchida: None. A. Watanabe: None. H. Takechi: None. Y. Nishida: None. H. Kumagai: None.
- © 2014 by American Heart Association, Inc.