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(Hypertension. 1999;34:176-180.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Early Onset Salt-Sensitive Hypertension in Bradykinin B₂ Receptor Null Mice

Ludek Cervenka; Lisa M. Harrison-Bernard; Susana Dipp; Ginny Primrose; John D. Imig; Samir S. El-Dahr

From the Departments of Pediatrics (S.D., S.S.E.-D.) and Physiology (L.C., L.M.H.-B., G.P., J.D.I.), Tulane University School of Medicine, New Orleans, La.

Correspondence to Samir S. El-Dahr, MD, Tulane University School of Medicine, Department of Pediatrics, SL-37, 1430 Tulane Ave, New Orleans, LA 70112-2699. E-mail seldahr{at}tmcpop.tmc.tulane.edu

Abstract—Kinins have been implicated in the hemodynamic adaptation to postnatal life. The present study examined the impact of bradykinin B₂ 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 HS 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.

Key Words: kallikrein-kinin system • renin-angiotensin system • receptors, bradykinin • blood pressure

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