Opposite regulation of brain and C-type natriuretic peptides in the streptozotocin-diabetic cardiopathy

C-type natriuretic peptide (CNP), a recent addition to the family of natriu retic peptides including atrial and brain natriuretic peptide (ANP, BNP), i s believed to be an endothelium-derived vasodilator and to have an antimito tic effect. ANP and BNP concentrations are increased in conditions such as congestive heart failure, but cardiac CNP concentrations have not been inve stigated in this connection. Diabetes mellitus also involves myocardial dys functions without coronary artery disease or systemic hypertension. We ther efore investigated the cardiac expression of CNP mRNA compared with that of BNP mRNA in streptozotocin (STZ)-diabetic rats. STZ- diabetic male Wistar rats (n=6) were studied in comparison with controls (n=6). The animals were characterised by their mean arterial blood pressure and plasma glucose con centrations. After extraction of total cardiac RNA, a specific cDNA probe o f BNP was used for northern blot analysis, whereas myocardial CNP expressio n was analysed by an RNase-protection assay. Twelve weeks after diabetes wa s induced, the rats were normotensive (96.4 +/- 2.0 compared with 95.1 +/- 1.9 mmHg) and hyperglycaemic (615 +/- 61 compared with 165 +/- 21 mg/dl; P< 0.001). Left ventricular pressure was significantly impaired (76.8 +/- 6.4 compared with 51.2 +/- 3.6 mmHg). STZ-diabetic rats had a 3.2-fold increase in cardiac BNP expression compared with controls. In contrast, cardiac CNP mRNA concentrations were decreased 2.6-fold. CNP seems to be downregulated like other peptides with antimitotic and vasodilator activities (nitric ox ide, prostacyclin, kinins). This may contribute to cardiac dysfunction in d iabetes mellitus and suggests that stimulation of CNP expression could prov ide cardiac protection in such cases.