Atrial natriuretic peptide (ANP), a 28 amino acid peptide hormone, is mainly synthesized by the atria and heart ventricles and is released in response to acute and chronic extracellular volume expansion. ANP facilitates the excretion of water and sodium and has a vasodilator effect on the blood vessels [1,2]. The release, storage and synthesis of ANP in the heart are intimately linked to changes in intravascular volume and blood pressure [3].Diabetes mellitus may lead to abnormalities in fluid and electrolyte balance and consequently affect blood volume and blood pressure [4]. Alterations in renin-angiotensin-aldosterone system and arginine vasopression (AVP) secretion, the two well-known mechanisms of controlling extracellular fluid volume homeostasis, have been observed both in humans with diabetes mellitus and in rats treated with alloxan [5]. Atrial natriuretic peptide also plays an important role in body fluid and electrolyte balances and in regulating blood pressure [1,2]. Plasma ANP concentrations have been reported to be either increased [6] or normal [7] in Type-I diabetic patients compared with normal subjects. Plasma ANP concentrations in chronic STZ-diabetic rats have also been shown to increase [8,9,10, 11] though unaltered plasma ANP concentrations have been reported [12,13]. It is still not clear whether the increased plasma ANP concentrations are due to increase in cardiac ANP secretion. Therefore, this study was to examine ANP content in the brain, the atria and the ventricles of the heart and the plasma. ANP mRNA expression in the atria and the ventricles were also quantified using solution-hybridization-RNase protection assay. Diabetologia (1998) Summary In rats with streptozotocin (STZ)-diabetes for 2 or 4 weeks, the atrial natriuretic peptide (ANP) concentrations in the atria decreased whilst that of ANP in the plasma and ventricles increased. ANP concentrations in the hypothalamus and in the brainstem did not change in either 2-or 4-week diabetic rats. Atrial ANP content was partly restored by insulin replacement in 4-week diabetic rats. Plasma ANP concentrations and ventricular ANP contents were reversed to normal by insulin treatment in both 2-and 4-week diabetic rats. Solution-hybridization-RNaseprotection assay showed a significant increase in the preproANP mRNA expression in the ventricles but not in the atria. These results indicated that the STZdiabetes increased the synthesis of ANP in the ventricles and consequently its release from the ventricles. The synthesis of ANP in the atria did not change as judged from the preproANP mRNA expression but the release of ANP from the atria might also be increased for ANP content decreased in the atria. The reason for the difference in the response of atrial and ventricular preproANP concentrations to STZ-diabetes is not known. [Diabetologia (1998) 41: 660±665]