Ludens J H, Clark M A, Lawson J A
Upjohn Laboratories, Kalamazoo, Michigan 49001, USA.
J Pharmacol Exp Ther. 1995 Jun;273(3):1375-81.
Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.
观察了钾通道阻滞剂对清醒大鼠肾小球滤过率和电解质排泄的影响。使用对三磷酸腺苷（ATP）敏感的钾通道阻滞剂4-吗啉甲脒-N-1-金刚烷基-N'-环己基盐酸盐（U-37883A），在先前已植入用于清除研究导管的清醒大鼠中，研究了钾通道调节对肾小球滤过率和电解质排泄的影响。在生理盐水负荷的大鼠中，静脉注射剂量为1.7、5.0和15 mg/kg的U-37883A可使钠排泄量的绝对值和分数剂量依赖性增加，而钾排泄量不变。利尿期间肾小球滤过率保持恒定。在水负荷（低渗葡萄糖）大鼠中，自由水清除率研究表明，在利钠活性高峰期，ATP敏感钾通道阻滞剂显著降低了稀释段溶质重吸收指标（经氯清除率校正的自由水清除率）。此外，U-37883A显著降低了肾乳头间质液的渗透压，表明在稀释段髓质部分有作用。这些发现共同表明，ATP敏感钾通道，可能是位于顶端边界的那些通道，在亨氏袢厚升支钠重吸收中起关键作用。
