Role of the bradykinin B2 receptor in the maturation of blood pressure phenotype: lesson from transgenic and knockout mice.
The binding of bradykinin (BK) to its B2 receptor results in a wide spectrum of biological effects including vasodilation, smooth muscle contraction and relaxation, pain, and inflammation. In order to gain a better insight into the physiological function of this potent vasoactive peptide, murine models have been created by the use of gene insertion or deletion. The results of studies using these strategies are revisited in the present article. In transgenic mice harboring the human BK B2 receptor cDNA (cHBKR), expression 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 injection of BK, whereas the blood pressure of knockout mice, homozygous for targeted disruption of the endogenous gene, was insensitive to BK. Two transgenic mouse lines expressing the human BK B2 receptor showed a significant reduction 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 B2 receptor knockout mice (124 +/- 1 mm Hg, n = 38). In heterozygous mice, systolic blood pressure was similar to that of controls until 5 month-old, then it raised to the elevated levels of knockout mice at 7 months of age. Together these data indicate that kinins acting through the B2 receptor play a role in the development of the blood pressure phenotype.
Madeddu
P
P
Department of Internal Medicine, University of Sassari, Italy. madeddu@ssmain.uniss.it
Emanueli
C
C
Gaspa
L
L
Salis
B
B
Milia
A F
AF
Chao
L
L
Chao
J
J
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology*; D008822:Mice, Transgenic / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000502:physiology*
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin