title: Effects of renal Na+/Ca2+ exchanger 1 inhibitor (SEA0400) treatment on electrolytes, renal function and hemodynamics in rats.
abstract: BACKGROUND
  Na(+)/Ca(2+) exchanger 1 (NCX1) controls intracellular Ca(2+) concentration in various cell types. In the kidney, NCX1 is expressed mainly in the distal tubular basolateral membrane as well as in vascular smooth muscle. Tubular NCX1 is involved in Ca(2+) reabsorption, and NCX1 in renal arterioles may control intraglomerular pressure. However, the functions of renal NCX1 have not been studied in vivo. Therefore, this study examined the effects of renal NCX1 blockade on water and solute metabolism, renal function and blood pressure in rats.
  
  
  METHODS
  Wistar-Kyoto rats were uninephrectomized, and an osmotic mini pump was implanted to infuse the remnant kidney cortex with a specific NCX1 inhibitor, SEA0400 (SEA), or vehicle for 7 days.
  
  
  RESULTS
  Serum Ca(2+) concentration and urinary Ca(2+) excretion were similar between the vehicle- and SEA-treated groups. However, serum phosphate was significantly decreased by 8 % in the SEA group, with similar urinary phosphate excretion between the two groups. Systolic blood pressure was higher in the SEA group (117 ± 3 vs. 126 ± 1 mmHg, n = 9-11), with a 1.6-fold increase in plasma aldosterone concentration. However, SEA significantly reduced urinary protein excretion and the glomerular sectional area by 16 and 8 %, respectively. Similar experiment in spontaneously hypertensive rats produced different results.
  
  
  CONCLUSIONS
  Renal SEA treatment reduced serum phosphate concentration, urinary protein and glomerular size with higher systemic blood pressure compared to control Wistar-Kyoto rats. Further study on renal NCX1 may be beneficial in delineating the pathophysiology of glomerular pressure control and calcium/phosphate regulations.
authors.affiliation: Department of Pharmacology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan, msasaki@fmu.ac.jp.
authors.forename: Midori Sasaki
authors.initials: MS
authors.lastname: Yatabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Yatabe
authors.forename: Kozue
authors.initials: K
authors.lastname: Takano
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sanada
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010647:Phenyl Ethers / Q000494:pharmacology*; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D002118:Calcium