Regulation of Potassium Excretion in FP Knockout Mice

Studies have suggested that PGF2a may play a role in K homeostasis. Urinary PGF2a, preferentially stimulated by an increased dietary K intake, has been shown to regulate Na absorption and K secretion. The purpose of this study is to determine if PGF2a regulates VUK through the FP receptor. Mice lacking the FP receptors (FP−/−) and wild type mice were fed normal chow (1.1% K, NK), a high K diet (5% K, HK), and a low K diet (0.07 % K, LK). The VUK and PK during the NK diet were similar in the FP −/− (703 ± 64 mEq and 4.45 ± 0.18 mEq/l, respectively) and the wild type (627 ± 67 mEq and 4.21 ± 0.11 mEq/l, respectively) mice. The FP −/− mice had a greater VUK (1918 ± 224 mEq) on the HK diet than the wild type mice (1623 ± 299 mEq). The PK during the HK diet increased in the FP−/− mice (5.23 ± 0.18 mEq/l, r< 0.001); but not in the wild type mice (4.63±0.23 mEq/l). The LK diet decreased the VUK and PK in the FP −/− (9.59 ± 1.40 μEq and 3.78 ± .26 mEq/l, respectively) and wild type (2.87 ± 0.45 μEq and 3.72 ± .41 mEq/l, respectively, r < 0.001) mice. FP−/− mice fed a LK diet exhibited a greater VUK indicating an inability to regulate K excretion. The aldosterone concentrations during NK and HK diets were greater in the FP−/− mice (354 ± 42 and 638 ± 63 rg/ml, respectively) than in the wild type mice (223 ± 45 and 401 ± 25 rg/ml, respectively). Quantitative RT‐PCR analysis indicated that the SGK‐1 expression was lower in the FP−/− mice than in the wild type mice. The SGK‐1 expression increased with the HK diet, but still remain lower in the FP−/− mice than in the wild type mice. The results of these studies lead us to conclude that the PGF2a via the FP receptor, in part, plays a role in K homeostasis.ααα