title: Conditional knockout of collecting duct bradykinin B2 receptors exacerbates angiotensin II-induced hypertension during high salt intake.
abstract: We elucidated the role of collecting duct kinin B2 receptor (B2R) in the development of salt-sensitivity and angiotensin II (ANG II)-induced hypertension. To this end, we used a Cre-Lox recombination strategy to generate mice lacking Bdkrb2 gene for B2R in the collecting duct (Hoxb7-Cre(tg/+):Bdkrb2(flox/flox)). In 3 groups of control (Bdkrb2(flox/flox)) and 3 groups of UB(Bdkrb2-/-) mice, systolic blood pressure (SBP) responses to high salt intake (4 or 8% NaCl; HS) were monitored by radiotelemetry in comparison with standard salt diet (0.4% NaCl) prior to and during subcutaneous ANG II infusion (1000 ng/min/kg) via osmotic minipumps. High salt intakes alone for 2 weeks did not alter SBP in either strain. ANG II significantly increased SBP equally in control (121 ± 2 to 156 ± 3 mmHg) and UB(Bdkrb2-/-) mice (120 ± 2 to 153 ± 2 mmHg). The development of ANG II-induced hypertension was exacerbated by 4%HS in both control (125 ± 3 to 164 ± 5 mmHg) and UB(Bdkrb2-/-) mice (124 ± 2 to 162 ± 3 mmHg) during 2 weeks. Interestingly, 8%HS caused a more profound and earlier ANG II-induced hypertension in UB(Bdkrb2-/-) (129 ± 2 to 166 ± 3 mmHg) as compared to control (128 ± 2 to 158 ± 2 mmHg) and it was accompanied by body weight loss and increased mortality. In conclusion, targeted inactivation of B2R in the renal collecting duct does not cause salt-sensitivity; however, collecting duct B2R attenuates the hypertensive actions of ANG II under conditions of very high salt intake.
authors.affiliation: a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic .
authors.forename: Libor
authors.initials: L
authors.lastname: Kopkan
authors.affiliation: a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic .
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Husková
authors.affiliation: a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic .
authors.forename: Šárka
authors.initials: Š
authors.lastname: Jíchová
authors.affiliation: a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic .
authors.forename: Lenka
authors.initials: L
authors.lastname: Červenková
authors.affiliation: a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine , Prague , Czech Republic .|b Department of Pathophysiology, 2nd Faculty of Medicine , Charles University , Prague , Czech Republic , and.
authors.forename: Luděk
authors.initials: L
authors.lastname: Červenka
authors.affiliation: c Department of Pediatrics , Tulane University School of Medicine , New Orleans , LA , USA.
authors.forename: Zubaida
authors.initials: Z
authors.lastname: Saifudeen
authors.affiliation: c Department of Pediatrics , Tulane University School of Medicine , New Orleans , LA , USA.
authors.forename: Samir S
authors.initials: SS
authors.lastname: El-Dahr
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007685:Kidney Tubules, Collecting / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*
chemical_list: D043782:Receptor, Bradykinin B2; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II
keywords: Angiotensin II; Cre recombinase; bradykinin receptor; collecting duct; high salt diet; hypertension; kallikrein–kinin system