Bk Gene Disruption Enhances Acute Renal Vascular Response To Angiotensin Ii

Renal vascular resistance is involved in the regulation of blood pressure through its contribution to the overall peripheral resistance and role in salt/fluid balance. Renal vascular tone is determined by the equilibrium between vasoconstrictive and vasodilative forces in renal arterial smooth muscle cells, where Angiotensin II type 1 receptor (AT1R) and BK channels are functionally coupled. In the present study, we investigated the role of BK in the maintenance of arterial blood flow and in its response to Angiotensin II (ANG II) stimulation. To this end, we used BK knockout (BK-/-) mice and ultrasound imaging to measure renal and aortic blood flow. In right renal arteries, peak systolic blood flow velocities (PSV) were similar in wild type, wt (502±122 mm/s, n=5) and BK-/- (482±64 mm/s, n=4) mice. End-diastolic velocities (EDV) also showed no differences (EDVwt=180±125 mm/s vs. EDVBK-/-=181±135 mm/s). Renal arterial resistive indexes (RI=[PSV-EDV]/PSV) appeared to be at the same level (RIwt=0.63±0.11, n=5 vs. RIBK-/-=0.63±0.05, n=4). Likewise, in abdominal aorta there were no significant differences in PSV, EDV, and RI. After administration of ANG II to wt mice (s.c., 500 ng/g body weight), right renal arterial PSV was reduced to 30.9±5.5% (n=6) of its initial value and recovered to 77.7±7.9% after 1 h. Remarkably, in BK-/- (n=3) PSV was reduced to 15.9±0.4%, and only recovered to 37.6±0.4% within the same time frame. Our findings show that loss of BK function does not cause alterations in basal arterial blood flow but critically potentiates the vasoconstrictor action of ANG II in renal arteries. Supported by NIH.