Hypotension in transgenic mice overexpressing human bradykinin B2 receptor.
Bradykinin binds to its receptor at target organs and exerts a wide spectrum of biological activities including vasodilation, smooth muscle contraction and relaxation, pain, and inflammation. To gain a better insight into the physiological function of this potent vasoactive peptide, we created transgenic mice that harbor the human bradykinin B2 receptor transgene under the control of the Rous sarcoma virus 3'-LTR promoter (RSV-cHBKR). Expression of HBKR in these transgenic mice was identified in the aorta, brain, heart, lung, liver, kidney, uterus, and prostate gland by reverse transcription-polymerase chain reaction Southern blot analysis. Two transgenic mouse lines expressing the human B2 receptor resulted in a significant reduction of blood pressure (84.2 +/- 0.6 mm Hg, n = 28; 76.9 +/- 0.8 mm Hg, n = 24; P < .001) compared with the control littermates (96.9 +/- 0.4 mm Hg, n = 52). Administration of Hoe 140, a bradykinin B2 receptor antagonist, restored the blood pressure of the transgenic mice to normal levels within 1 hour, and the effect diminished within 4 hours. The transgenic mice displayed enhanced blood pressure-lowering effect induced by a bolus intra-aortic injection of kinin and showed increased response in kinin-induced uterine smooth muscle contractility compared with control littermates. These studies show that overexpression of human bradykinin B2 receptor causes a sustained reduction of blood pressure in transgenic mice. They also suggest that the B2 receptor-mediated signal transduction pathway plays a role in blood pressure regulation.
Wang
D Z
DZ
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
Chao
L
L
Chao
J
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002460:Cell Line; D005260:Female; D006801:Humans; D007022:Hypotension / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000502:physiology; D010641:Phenotype; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D014162:Transfection; D014590:Uterine Contraction
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin