Contractile Force Is Enhanced in Aortas from Pendrin Null Mice Due to Stimulation of Angiotensin II-Dependent Signaling

• Type of Material: Article
• Authors: Roy Sutliff, Emory University; Erik R. Walp Walp, Emory University; Young Hee Kim, Emory University; Lori A. Walker, University of Colorado; Alexander M. El-Ali, Emory University; Jing Ma, Emory University; Robert Bonsall, Emory University; Semra Ramosevac, Emory University; Douglas Eaton, Emory University; Jill W. Verlander, University of Florida; Laura Hansen, Georgia Institute of Technology; Rudolph L. Jr. Gleason, Georgia Institute of Technology; Truyen D. Pham, Emory University; Seongun Hong, Emory University; Vladimir Pech, Emory University; Susan Wall, Emory University
• Language: English
• Date: 2014-08-22
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Sutliff et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0105101
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 8
• Start Page: e105101
• End Page: e105101
• Grant/Funding Information: The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.; Funding provided by National Institute of Diabetes, Digestive and Kidney Diseases grants 46493 (to S. M. Wall); 37963 (to D. C. Eaton); and National Heart, Lung and Blood Institute grant 070892 (to R. L. Sutliff).
• Keywords: BLOOD-PRESSURE; HEAVY-CHAIN; ALDOSTERONE-SALT HYPERTENSION; C57BL/6J MOUSE; MYOCARDIAL-ISCHEMIA; Multidisciplinary Sciences; Science & Technology - Other Topics; INTERCALATED CELLS; Science & Technology; ISOMETRIC FORCE; MOUSE KIDNEY; PSYCHOPHYSIOLOGICAL INVESTIGATIONS; VASCULAR SMOOTH-MUSCLE
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, General

Abstract

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation.