Natriuretic effects of urocuamylin in the isolated perfused rat kidney

The discover)' of receptor-guanylate cyclases activated by E. coli heat-stable enterotoxin (STa) in the kidney culminated with the isolation of uroguanylin from opossum urine. Because uroguanylin is made in the intestinal mucosa, we postulated that this peptide serves as an intestinal natriuretic hormone. Isolated kidneys were prepared from male Wistar rats and perfused with Krebs-Henseleit solution containing 6% BSA. At 10 min intervals, perfusion pressure, urine flow, GFR. electrolytes and osmolar and free water clearances were measured. Uroguanylin was added after a 30 min control period. The results demonstrated that uroguanylin increases urine flow and GFR while raising perfusion pressure by 10 to 30% (p<0.05) at concentrations of 0.3, 1 and 3 μg/ml. Uroguanylin also promoted a dose-related natriuresis, reducing the tubular Na⁺ reabsorption from 80% to 50% (p<0.01). a response that lasted for 90 min. Kaliuresis was also observed and uroguanylin increased the osmolar clearance, Uroguanylin is 10 to 100-fold more potent than guanylin and 10-fold less potent than E. coli STa in this preparation as a nalriuretic agent. We conclude that uroguanylin is a potent diuretic and nafriuretic agent in the isolated perfused rat kidney and that this hormone, though made predominantly by the intestinal mucosa has a role in regulating salt and water homeostasis through its actions in the kidney.