Role of the bradykinin B-2 receptor in the maturation of blood pressure phenotype, lesson from transgenic and knockout mice

The binding of bradykinin (BK) to its B-2 receptor results in a wide spectr um of biological effects including vasodilation, smooth muscle contraction and relaxation, pain, and inflammation. In order to gain a better insight i nto the physiological function of this potent vasoactive peptide, murine mo dels have been created by the use of gene insertion or deletion. The result s of studies using these strategies are revisited in the present article. I n transgenic mice harboring the human BK B-2 receptor cDNA (cHBKR), express ion of the transgene was identified in the aorta, brain, heart, lung, liver , kidney, uterus and prostate gland by RT-PCR Southern blot analysis. These mice displayed an exaggerated hypotensive response to intra-aortic injecti on of BK, whereas the blood pressure of knockout mice, homozygous for targe ted disruption of the endogenous gene, was insensitive to BK. Two transgeni c mouse lines expressing the human BK B-2 receptor showed a significant red uction of systolic tail-cuff blood pressure (84 +/- 1 mm Hg, n = 28; 80 +/- 1 mm Hg, n = 24; P < 0.001) compared with the control littermates (97 +/- 1 mm Hg, n = 52). Systolic blood pressure was elevated in BK B-2 receptor k nockout mice (124 +/- 1 mm Hg, n = 38). In heterozygous mice, systolic bloo d pressure was similar to that of controls until 5 month-old, then it raise d to the elevated levels of knockout mice at 7 months of age. Together thes e data indicate that kinins acting through the B-2 receptor play a role in the development of the blood pressure phenotype. (C) 1999 Elsevier Science B.V. All rights reserved.