Early onset salt-sensitive hypertension in bradykinin B2 receptor null mice

Kinins have been implicated in the hemodynamic adaptation to postnatal life. The present study examined the impact of bradykinin B-2 receptor (B2R) gene disruption on the postnatal changes in blood pressure (BP) and the susceptibility to early onset salt-sensitive hypertension in mice. B2R null (-/-) and wild-type (+/+) mice were fed normal (NS, 1% NaCl) or high (HS, 5% NaCl) salt diets during pregnancy. After birth, the pups remained with their mothers until they were weaned and were subsequently continued on the respective maternal salt intake until 4 months of age. The age-related changes at 3 and 4 months in tail-cuff BP and anesthetized mean arterial pressure at 4 months were not different in NS/B2R-/- and NS/B2R+/+ mice. However, there was a mild increase in BP in NS/B2R-/- at 2 months versus NS/B2R+/+. In contrast, HS/B2R-/- mice manifested early onset and persistent elevations of tail-cuff BP (P < 0.05) at 2, 3, and 4 months versus other groups. MAP was also higher in HS/B2R-/- than HS/B2R+/+, NS/B2R-/- and NS/B2R+/+ (91 +/- 3 versus 75 +/- 5, 74 +/- 2, and 70 +/- 2 mm Hg, respectively; P < 0.05). Kidney renin and angiotensin type 1 receptor mRNA levels were not different. Additional studies showed that a delay in the initiation of NS until after birth was accompanied by later development of hypertension, although postnatal discontinuation of HS resulted in a gradual return of BP to normal values by 4 months of age. The results demonstrate that (1) kinins protect the developing animal from salt-sensitive hypertension, (2) lack of B2R from early development does not alter the maturation of BP under conditions of normal sodium intake, and (3) exposure to a HS diet during fetal life is not sufficient in itself to induce long-term hypertension in either wild-type or B2R null mice.