Enhanced renal function in bradykinin B(2) receptor transgenic mice.
The tissue kallikrein-kinin system has been recognized as a paracrine and/or autocrine hormonal system that regulates arterial pressure, renal hemodynamics, and electrolyte excretion. We have created a transgenic mouse model overexpressing human bradykinin B(2) receptor, and the mice developed lifetime hypotension. With this animal model, we further analyzed the potential role of B(2) receptors in regulation of renal function. Baseline urinary excretion, urinary potassium excretion, and pH were significantly increased in transgenic mice, whereas urinary sodium excretion and serum sodium concentration were unaltered. Transgenic mice exhibited increased renal blood flow, glomerular filtration rate, and urine flow. Enhanced renal function was accompanied by significant increases in urinary nitrate/nitrite, cGMP, and cAMP levels with unaltered urinary kinin levels in transgenic mice compared with control siblings. Renal cGMP and cAMP content was also significantly increased in transgenic mice. Because the renin-angiotensin system exerts vasoconstriction buffering vasodilation of the kallikrein-kinin system, expression of renin-angiotensin components was examined by Northern blot analysis. We found a significant increase in hepatic angiotensinogen expression with no changes in renal renin and pulmonary angiotensin-converting enzyme mRNA levels in B(2) receptor transgenic mice. These studies showed that overexpression of B(2) receptors in transgenic mice resulted in hypotension and enhanced renal function through activation of nitric oxide-cGMP and cAMP signal transduction pathways.
Wang
D
D
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Yoshida
H
H
Song
Q
Q
Chao
L
L
Chao
J
J
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000652:urine; D006152:Cyclic GMP / Q000378:metabolism / Q000652:urine; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D007705:Kinins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology
D007705:Kinins; D009566:Nitrates; D009573:Nitrites; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D000242:Cyclic AMP; D006152:Cyclic GMP