Vallon V, Kirschenmann D, Brenner I, Albinus M, Osswald H
Department of Pharmacology, University of Tübingen, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Aug;358(2):245-52. doi: 10.1007/pl00005249.
The role of potassium intake in the response of kidney function and plasma renin activity (PRA) to systemic application of U37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl-hydro chloride), a putative blocker of ATP-sensitive potassium channels (K(ATP)), and P1075 (N-cyano-N'-(1,1-dimethylpropyl)-N"-pyridylguanidine), an opener of K(ATP) channels, was studied in the anesthetized rat. It was found that under normal potassium diet (0.7% K), U37883A (15 mg/kg, i.v.) increased urinary flow rate (UV) and sodium excretion (UNaV), decreased urinary potassium excretion (UKV), and significantly diminished heart rate (HR) without affecting mean arterial blood pressure (MAP) or glomerular filtration rate (GFR). P1075 (10 microg/kg, i.v.) lowered UV, UNaV and UKV, at least in part due to the fall in MAP and GFR. PRA was diminished by U37883A and increased by P1075. Variation in potassium diet (0.04 or 2% K) left the response in MAP, HR or GFR to both potassium channel modulators essentially unchanged. The reduction in renal excretion rates to P1075 also appeared unaffected, further supporting a predominant role of the change in MAP and GFR in this response. Variation in potassium diet, however, elicited the following alterations: (1) under both low and high potassium diet U37883A did no longer cause a significant natriuresis; (2) U37883A elicited a significant kaliuresis under high potassium diet, whereas potassium excretion remained essentially unchanged on very low levels under low potassium diet; (3) the increase in PRA to P1075 was blunted under low potassium diet. Additional experiments provided evidence that P1075 releases renin from freshly isolated juxtaglomerular cells of rats on normal but not on low potassium diet. In summary, systemic potassium channel modulation employing U37883A or P1075, respectively, exerts distinct effects on blood pressure and heart rate independent of potassium diet. In contrast, potassium diet appears to be a determinant for the concomitant responses in plasma renin activity and renal sodium and potassium excretion.
在麻醉大鼠中研究了钾摄入在肾功能及血浆肾素活性（PRA）对全身应用U37883A（4 - 吗啉甲脒 - N - 1 - 金刚烷基 - N'-环己基 - 盐酸盐，一种推测的ATP敏感性钾通道（K(ATP)）阻滞剂）和P1075（N - 氰基 - N' - (1,1 - 二甲基丙基) - N" - 吡啶基胍，一种K(ATP)通道开放剂）反应中的作用。发现在正常钾饮食（0.7% K）条件下，U37883A（15 mg/kg，静脉注射）增加尿流率（UV）和钠排泄（UNaV），降低尿钾排泄（UKV），并显著降低心率（HR），而不影响平均动脉血压（MAP）或肾小球滤过率（GFR）。P1075（10 μg/kg，静脉注射）降低UV、UNaV和UKV，至少部分原因是MAP和GFR下降。U37883A降低PRA，P1075升高PRA。钾饮食变化（0.04%或2% K）使MAP、HR或GFR对两种钾通道调节剂的反应基本不变。P1075引起的肾排泄率降低似乎也未受影响，这进一步支持了MAP和GFR变化在此反应中的主要作用。然而，钾饮食变化引起了以下改变：（1）在低钾和高钾饮食条件下，U37883A均不再引起显著的利钠作用；（2）U37883A在高钾饮食条件下引起显著的尿钾增多，而在低钾饮食条件下极低水平时钾排泄基本不变；（3）低钾饮食条件下P1075引起的PRA升高减弱。额外实验提供的证据表明，P1075在正常钾饮食而非低钾饮食条件下可从新鲜分离的大鼠球旁细胞释放肾素。总之，分别使用U37883A或P1075进行全身钾通道调节对血压和心率产生独立于钾饮食的不同影响。相反，钾饮食似乎是血浆肾素活性以及肾钠和钾排泄伴随反应的一个决定因素。
