Department of Medicine, Unit of Internal Medicine B, University of Verona, Verona, Italy.
Hypertens Res. 2013 Jun;36(6):528-33. doi: 10.1038/hr.2012.232. Epub 2013 Jan 24.
Prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease, activates the epithelial sodium (Na) channel (ENaC), and prostasin is released in extracellular fluids, including urine. Previous data have suggested a direct association between urinary prostasin and the activation of an aldosterone-driven pathway, but a quantitative association has never been demonstrated in normotensive subjects. Similarly, physiological relationships with natriuresis or possible gender- or female hormone-related changes in urinary prostasin concentrations have never been investigated. We measured urinary prostasin by enzyme-linked immunosorbent assay in 43 healthy normotensive subjects of similar age presenting different urinary Na levels and in 15 women during the menstrual cycle and after oral estro-progestinic contraceptive (OC) therapy. Exosomal urinary prostasin was also estimated by western blotting of samples from six healthy subjects twice during the morning. Urinary prostasin presented a wide range of values (from 0.5 to 18.9 nM) without gender differences. It was positively correlated with the aldosterone to renin ratio (ARR) but not with circulating aldosterone or renin individually. Urinary prostasin was directly correlated with U-Na levels (up to 200 nmol Na), whereas it decreased for higher Na concentrations. In women, no significant changes of prostasin concentration were observed during menstrual phases. After OC therapy, prostasin increased (from 2.37±1.27 to 4.85±5.28 nM), although the increase was not statistically different (P=0.07). Prostasin was detectable in urinary exosomes and displayed a pattern similar to urinary prostasin in relation to urinary Na. In conclusion, urinary prostasin correlates with the ARR, and it is physiologically modulated by natriuresis in normotensive individuals.
前列腺素，一种糖基磷脂酰肌醇（GPI）锚定的丝氨酸蛋白酶，激活上皮钠（Na）通道（ENaC），并在细胞外液中释放，包括尿液。先前的数据表明，尿前列腺素与醛固酮驱动途径的激活之间存在直接关联，但在正常血压受试者中从未证明过定量关联。同样，尿前列腺素与利钠作用的生理关系，或其浓度在性别或女性激素相关的变化，也从未被研究过。我们通过酶联免疫吸附试验（ELISA）在 43 名年龄相似、尿 Na 水平不同的健康正常血压受试者和 15 名女性月经周期和口服雌激素孕激素避孕药（OC）治疗期间测量了尿前列腺素。还通过对来自 6 名健康受试者的样本进行两次western 印迹分析，估算了尿前列腺素的外泌体。尿前列腺素的数值范围很广（0.5-18.9 nM），无性别差异。它与醛固酮与肾素比值（ARR）呈正相关，但与单独的循环醛固酮或肾素无关。尿前列腺素与 U-Na 水平直接相关（高达 200 nmol Na），但在更高的 Na 浓度下则下降。在女性中，月经期间未观察到前列腺素浓度的显著变化。OC 治疗后，前列腺素增加（从 2.37±1.27 增加到 4.85±5.28 nM），尽管增加无统计学差异（P=0.07）。尿外泌体中可检测到前列腺素，其与尿 Na 的关系与尿前列腺素的模式相似。总之，尿前列腺素与 ARR 相关，并在正常血压个体中受到利钠作用的生理调节。
