Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Autor: Sutliff RL; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Walp ER; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Kim YH; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Walker LA; Departments of Medicine and Cardiology, University of Colorado Health Sciences Center, Aurora, Colorado, United States of America., El-Ali AM; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Ma J; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, United States of America; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Bonsall R; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, United States of America., Ramosevac S; Department of Physiology, Emory University, Atlanta, Georgia, United States of America., Eaton DC; Department of Physiology, Emory University, Atlanta, Georgia, United States of America., Verlander JW; Department of Medicine, University of Florida, Gainesville, Florida, United States of America., Hansen L; School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America., Gleason RL Jr; School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America., Pham TD; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Hong S; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Pech V; Department of Medicine, Emory University, Atlanta, Georgia, United States of America., Wall SM; Department of Medicine, Emory University, Atlanta, Georgia, United States of America; Department of Physiology, Emory University, Atlanta, Georgia, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Aug 22; Vol. 9 (8), pp. e105101. Date of Electronic Publication: 2014 Aug 22 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0105101
Abstrakt: 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.
Databáze: MEDLINE
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