The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin.
Angiotensin converting enzyme (ACE) inhibition leads to increased levels of bradykinin, cyclooxygenase-2 (COX-2), and renin. Since bradykinin stimulates prostaglandin release, renin synthesis may be regulated through a kinin-COX-2 pathway. To test this hypothesis, we examined the impact of bradykinin B2 receptor (B2R) gene disruption in mice on kidney COX-2 and renin gene expression. Kidney COX-2 mRNA and protein levels were significantly lower in B2R-/- mice by 40-50%. On the other hand, renal COX-1 levels were similar in B2R-/- and +/+ mice. Renal renin protein was 61% lower in B2R-/- compared to B2R+/+ mice. This was accompanied by a significant reduction in renin mRNA levels in B2R-/- mice. Likewise, intrarenal angiotensin I levels were significantly lower in B2R-/- mice compared to B2R+/+ mice. In contrast, kidney angiotensin II levels were not different and averaged 261+/-16 and 266+/-15fmol/g in B2R+/+ and B2R-/- mice, respectively. Kidney angiotensinogen, AT1 receptor and ACE activity were not different between B2R+/+ and B2R-/- mice. The results of these studies demonstrate suppression of renal renin synthesis in mice lacking the bradykinin B2R and support the notion that B2R regulation of COX-2 participates in the steady-state control of renin gene expression.
Imig
John D
JD
Department of Physiology, Medical College of Georgia, Vascular Biology Center, Augusta, GA 30912-2500, USA. jdimig@mail.mcg.edu
Zhao
Xueying
X
Orengo
Sheyla R
SR
Dipp
Susana
S
El-Dahr
Samir S
SS
D000803:Angiotensin I / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D005786:Gene Expression Regulation / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D012083:Renin / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D000803:Angiotensin I; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin