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 Cretg/:Bdkrb2flox/flox) In 3 groups of control (Bdkrb2flox/flox) and 3 groups of UBBdkrb2 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 UBBdkrb2 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 UBBdkrb2 mice (124 2 to 162 3 mmHg) during 2 weeks. Interestingly, 8%HS caused a more profound and earlier ANG II induced hypertension in UBBdkrb2 (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.
Clinical and experimental hypertension