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The Development of Angiotensin II ‐ induced Hypertension During Various Salt Intakes in Cre/lox Conditional Knockout Mice for Bradykinin Receptors in The Collecting Duct
Author(s) -
Kopkan Libor,
Huskova Zuzana,
Jichova Sarka,
Cervenka Ludek,
Saifudeen Zubaida,
ElDahr Samir
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.960.13
Subject(s) - bradykinin , medicine , endocrinology , blood pressure , angiotensin ii , chemistry , receptor , knockout mouse , renin–angiotensin system
Bradykinin is an important antihypertensive peptide acting mostly via the kinin B 2 receptor (gene: Bdkrb2; protein: B 2 R). We elucidated the role of collecting duct B 2 R in the development of salt‐sensitivity and angiotensin II (ANG II)‐induced hypertension. We used a Cre‐Lox recombination strategy to generate mice lacking Bdkrb2 gene for B 2 R 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 pumps. 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 B 2 R in the collecting duct does not cause salt‐sensitivity; however, collecting duct B 2 R attenuates the hypertensive actions of ANG II action under conditions of very high salt intake.