title: Ablation of Potassium-Chloride Cotransporter Type 3 (Kcc3) in Mouse Causes Multiple Cardiovascular Defects and Isosmotic Polyuria.
abstract: Inactivation of Kcc3 in a mixed 129/Sv×C57BL/6 mouse background has been previously found to increase systemic blood pressure (BP) through presumed neurogenic mechanisms. Yet, while this background is generally not considered ideal to investigate the cardiovascular system, KCC3 is also expressed in the arterial wall and proximal nephron. In the current study, the effects of Kcc3 ablation was investigated in a pure rather than mixed C57BL/6J background under regular- and high-salt diets to determine whether they could be mediated through vasculogenic and nephrogenic mechanisms. Aortas were also assessed for reactivity to pharmacological agents while isolated from the influence of sympathetic ganglia. This approach led to the identification of unforeseen abnormalities such as lower pulse pressure, heart rate, aortic reactivity and aortic wall thickness, but higher diastolic BP, left ventricular mass and urinary output in the absence of increased catecholamine levels. Salt loading also led systolic BP to be higher, but to no further changes in hemodynamic parameters. Importantly, aortic vascular smooth muscle cells and cardiomyocytes were both found to express KCC3 abundantly in heterozygous mice. Hence, Kcc3 inactivation in our model caused systemic vascular resistance and ventricular mass to increase while preventing extracellular fluid volume to accumulate. Given that it also affected the physiological properties of aortas in vitro, vasculogenic mechanisms could therefore account for a number of the hemodynamic abnormalities observed.
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Garneau
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Andrée-Anne
authors.initials: AA
authors.lastname: Marcoux
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Micheline
authors.initials: M
authors.lastname: Noël
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Frenette-Cotton
authors.affiliation: Valvulopathy Research Group, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.affiliation: Valvulopathy Research Group, Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Larivière
authors.affiliation: Nephrology Research Group, Centre de recherche L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, Québec City, Canada.|Department of Medicine, Université Laval, Québec City, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Isenring
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D017353:Gene Deletion; D006321:Heart / Q000503:physiopathology; D006334:Heart Function Tests; D006439:Hemodynamics; D006728:Hormones / Q000378:metabolism; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D008810:Mice, Inbred C57BL; D009995:Osmosis; D011141:Polyuria / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics; D000096922:K Cl- Cotransporters
chemical_list: D006728:Hormones; D008055:Lipids; D012964:Sodium; D027981:Symporters; C492280:Slc12a6 protein, mouse; D000096922:K Cl- Cotransporters