Elevated atrial natriuretic peptides and early renal failure in type 2 diabetic Goto-Kakizaki rats

The present investigation was designed to determine if atrial natriuretic p eptides (ANPs) are increased in a spontaneous model of non-obese type 2 dia betes, the Goto-Kakizaki (GK) rat. Four peptide hormones originating from t he ANP prohormone were increased twofold (P <.05) to sixfold (P <.01) in th e circulation of GK rats compared with nondiabetic Wistar rats from which t he GK colony was originally derived. Thus, ANP. long-acting natriuretic pep tide (LANP). vessel dilator, and kaliuretic peptide were (mean +/- SE) 497 +/- 78, 1,285 +/- 105, 457 +/- 45, and 385 +/- 87 pg/mL in GK rats, versus 78 +/- 23, 542 +/- 77, 137 +/- 26, and 134 +/- 33 pg/mL, respectively, in W ister rats. In evaluating the cause of the increased ANPs. the blood volume of Oh rats (16.2 +/- 0.4 mL) was significantly (P <.01) increased compared with Wistar rats (9.5 +/- 0.3 mt). The ventricles of GK rats were not dila ted when examined by transthoracic echocardiography, but the venous system was markedly distended. Oh rats had a 48% to 79% decrease in renal function (ie, increased serum creatinine and blood urea nitrogen [BUN]) compared wi th Wistar rats. These results indicate that circulating ANPs are increased in the GK spontaneously diabetic rat secondary to (1) increased blood volum e, which leads to increased synthesis and release of ANPs, and (2) renal fa ilure, which results in a delayed metabolic processing of these peptides. T he early combined increases of the four atrial peptides collectively may co ntribute to the hyperfiltration that occurs in early diabetes mellitus. Cop yright (C) 1999 by W.B. Saunders Company.