Effects of chronic octreotide treatment on renal changes during cirrhosis in rats

We examined the effect of a new long-acting release formula (LAR) of the so matostatin analogue, octreotide, on development of sodium retention and fun ctional and structural changes in the thick ascending limb of Henle's loop (TAL) in rats with cirrhosis induced by common bile duct ligation (CBL), CB L and sham-operated control rats were treated with octreotide-LAR (10 mg/kg body weight subcutaneously, as a single dose) or vehicle at the time of CB L or sham-CBL, The rats were instrumented with chronic catheters, and sodiu m balance and renal function were examined 4 weeks after CBL or sham operat ion. Octreotide-LAR treatment significantly inhibited sodium retention in C BL rats and prevented renal vasodilatation without changes in glomerular fi ltration rate (GFR), The natriuretic response to a test dose of furosemide (7.5 mg/kg body weight intravenously) was significantly increased in CBL ra ts, and when expressed in terms of natriuretic efficiency (mmol Na/mg furos emide in urine), the natriuretic response was increased by 57% relative to sham-operated controls. Stereological examination of kidneys demonstrated a 53% increase in the volume of the inner stripe of the outer medulla and a 108% increase in the volume of TAL epithelium in cirrhotic rats relative to controls. The increased natriuretic efficiency of furosemide as well as th e hypertrophy of the inner stripe and the TAL in this renal zone were absen t in CBL rats treated with octreotide-LAR. These results suggest that octre otide-LAR treatment inhibits sodium retention in cirrhotic rats, partly by inhibition of increased furosemide-sensitive sodium reabsorption in the TAL .