Effects of somatostatin and captopril on glomerular prostaglandin E2 production in normal and diabetic rats.
Somatostatin (SRIH) has recently been shown to be effective in reversing many of the early changes of diabetic nephropathy. It is unknown whether SRIH exerts its protective effects via its ability to suppress growth hormone (GH) or via other direct renal effects. Since changes in glomerular prostaglandin (PG) E2 production are thought to be an important part of the underlying pathophysiology of diabetic nephropathy, we sought to determine if SRIH altered glomerular PG E2 production in the rat. Whole glomeruli isolated from streptozotocin-diabetic rats and from controls were incubated with either saline, captopril, or varying concentrations of SRIH, and PG E2 production was determined by direct radioimmunoassay of media. Incubation with captopril (10(-4) M) resulted in equivalent increases in PG E2 production in glomeruli from both control and diabetic rats (140.8 +/- 12.8% and 150.2 +/- 18.9% respectively). Incubation with high concentrations of SRIH (10(-6) M) also resulted in significant increases in glomerular PG E2 production in both diabetic and control rats. However, at low SRIH concentrations (10(-10) M), glomerular PG E2 production was increased only in the diabetic rats (167.0 +/- 11.4% vs 95.3 +/- 9.2% in normals). We conclude that SRIH increases glomerular PG E2 production, and that glomeruli from diabetic rats appear to be more sensitive to lower concentrations of SRIH when compared to normal rats. It is possible that this effect on PG E2 production may underlie the favorable effects of SRIH on the glomerulus in diabetes.
Nickels
D
D
Department of Pediatrics, Walter Reed Army Medical Center.
Schwab
N
N
Poth
M
M
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin; D002216:Captopril; D015232:Dinoprostone