| First Author | Wang B | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | Volume | 316 |
| Issue | 2 | Pages | F341-F350 |
| PubMed ID | 30484346 | Mgi Jnum | J:280227 |
| Mgi Id | MGI:6369106 | Doi | 10.1152/ajprenal.00223.2018 |
| Citation | Wang B, et al. (2019) Furosemide reduces BK-alphabeta4-mediated K(+) secretion in mice on an alkaline high-K(+) diet. Am J Physiol Renal Physiol 316(2):F341-F350 |
| abstractText | Special high-K diets have cardioprotective effects and are often warranted in conjunction with diuretics such as furosemide for treating hypertension. However, it is not understood how a high-K diet (HK) influences the actions of diuretics on renal K(+) handling. Furosemide acidifies the urine by increasing acid secretion via the Na(+)-H(+) exchanger 3 (NHE3) in TAL and vacuolar H(+)-ATPase (V-ATPase) in the distal nephron. We previously found that an alkaline urine is required for large conductance Ca(2+)-activated K(+) (BK)-alphabeta4-mediated K(+) secretion in mice on HK. We therefore hypothesized that furosemide could reduce BK-alphabeta4-mediated K(+) secretion by acidifying the urine. Treating with furosemide (drinking water) for 11 days led to decreased urine pH in both wild-type (WT) and BK-beta4-knockout mice (BK-beta4-KO) with increased V-ATPase expression and elevated plasma aldosterone levels. However, furosemide decreased renal K(+) clearance and elevated plasma [K(+)] in WT but not BK-beta4-KO. Western blotting and immunofluorescence staining showed that furosemide treatment decreased cortical expression of BK-beta4 and reduced apical localization of BK-alpha in connecting tubules. Addition of the carbonic anhydrase inhibitor, acetazolamide, to furosemide water restored urine pH along with renal K(+) clearance and plasma [K(+)] to control levels. Acetazolamide plus furosemide also restored the cortical expression of BK-beta4 and BK-alpha in connecting tubules. These results indicate that in mice adapted to HK, furosemide reduces BK-alphabeta4-mediated K(+) secretion by acidifying the urine. |
