Kinins are vasodilatory and natriuretic paracrine agents involved in the regulation of blood pressure and volume homeostasis. This study examined the consequences of high salt intake during early development on the adult arterial pressure phenotype in mice with homozygous deletion of the B2R gene (B2R-KO). Pregnant B2R-KO and C57B16 wild-type (WT) mice were fed high (HS, 5%) or normal (NS, 1%) salt-isocaloric diets until weaning(day 21). The pups continued on the maternal salt intake until 4 months of age. Conscious systolic blood pressures (SBP) were measured using tail-cuff apparatus at 2, 3, and 4 months of age. HSB2R-KO mice exhibited an augmented developmental rise in SBP compared to the other groups (p<0.05). SBP was 30% higher in HSB2R-KO than HSWT mice (126±5 vs 96±7 mmHg, p<0.05; N=12, 7), while not different in NSB2R-KO and NSWT (98±5 vs 102±7 mmHg, N=4, 6) at 4 months. Anesthetized mean arterial pressure (MAP) was higher in HSB2R-KO than HSWT, NSB2R-KO and NSWT (91±3 vs 75±5, 74±2 and 70±2, respectively, p<0.05). Angiotensin II (50 ng, iv) caused a similar rise in MAP in all groups, indicating that angiotensin II vascular responses are maintained in the 4 groups. However, the AT1R antagonist, Candesartan (1mg/kg, i.v.), caused a profound drop in MAP in HSB2R-KO compared to HSWT mice (-29±6 vs. -6±2 mmHg, p<0.05) suggesting a failure to appropriately suppress angiotensin II activity by chronic high salt in HSB2R-KO mice. In conclusion, life-long high salt intake causes hypertension in mice lacking the bradykinin B2R indicating that endogenous kinins protect against salt sensitivity. In addition, dysregulation of the reninangiotensin system may contribute to the pathogenesis of salt sensitivity in B2R-KO mice.
