NATRIURETIC AND KALIURETIC ACTIVITIES OF GUANYLIN AND UROGUANYLIN IN THE ISOLATED-PERFUSED RAT-KIDNEY

Guanylin and uroguanylin are novel peptides that activate membrane gua nylate cyclases found in the kidney and intestine. We compared the eff ects of these peptides in the isolated perfused rat kidney. Both pepti des are natriuretic and kaliuretic in this preparation. Uroguanylin (0 .19-1.9 mu M) increased glomerular filtration rate from 0.77 +/- 0.07 to 1.34 +/- 0.3 ml.g(-1).min(-1) at the highest concentration. A maxim al increase in Na+ excretion was achieved at 0.66 mu M uroguanylin, wi th a reduction in fractional Na+ reabsorption from 78.7 +/- 1.7 to 58. 8 +/- 4.4%. The highest dose of uroguanylin increased kaliuresis by 50 %. Osmolar clearance doubled at the highest concentration of uroguanyl in tested (P < 0.05). Guanylin also elicited a natriuresis and kaliure sis but appeared to be less potent than uroguanylin. The highest conce ntration of guanylin (1.3 mu M) decreased fractional Na+ reabsorption from 73.9 +/- 2.4 to 64.5 +/- 4.0%, but lower doses were ineffective. Guanylin stimulated urine K+ excretion at the lowest concentration tes ted (0.33 mu M) without any effect on Na+ excretion. These peptides ma y influence salt and water homeostasis by biological effects in the ki dney that are mediated by the intracellular second messenger, cGMP.