Abstrakt
The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)-induced hypertension in mice. BK B-2 receptor knockout (B2R-/-) and wild-type (B2R+/+) mice (22 to 26 g) were infused with either saline (SAL) or Ang II (40 ng/min) via an osmotic minipump implanted intraperitoneally.
On day 12 after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B2R+/+ and SAL/B2R-/- mice (128+/-5 versus 133+/-6 mm Hg, n=24/oroup). In contrast, SEP was higher on day 12 of infusion in Ang II/B2R-/- than in Ang II/B2R+/+ mice (173+/-6 versus 156+/-5 mm Hg; Pg.g(-1).min(-1)) in SAL/B-2(+/+) and SAL/B-2(-/-) mice caused equal increases in MAP (142+/-1 versus 145 +/- 1 mm Hg) and decreases in RPF (2.06+/-0.06 versus 2.12 +/- 0.15 mL.min(-1).g(-1)).
However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B2R+/+ mice than of Ang II/B2R-/- mice, such that MAP after NOS inhibition in Ang II/B2R+/+ approached that of Ang II/B2R-/- mice (156+/-2 versus 159+/-2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B2R+/+ mice to values similar to those of Ang II/B2R-/- mice before NOS inhibition (2.12+/-0.09 versus 2.34+/-0.06 mL.min(-1).g(-1)).
These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B2R-/- mice to Ang II-induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.