Upregulation of ANP and NPR-C mRNA in the kidney and heart of eNOS knockout mice.

OBJECTIVES

The aim of the present studywas to examine the question of whether the atrial natriuretic peptide (ANP) system is altered by endothelial nitric-oxide synthase (eNOS).

METHODS

Male eNOS-deficient mice (eNOS-/-) and wild type control mice (eNOS+/+, C57B1/6J) were used. Blood pressure was measured in anesthetized mice by tail cuff plethysmography and renal function was measured. Expression of ANP, natriuretic peptide receptor (NPR)-A, NPR-C, and tonicity-responsive enhancer binding protein (TonEBP) mRNA was determined by real-time PCR. Localization of (125)I-ANP binding sites was measured using in vitro autoradiography.

RESULTS

In eNOS-/- mice, systolic blood pressure increased and left ventricular hypertrophy was observed. Urine volume and osmolarity did not change. Expression of ANP markedly increased in the heart and kidney of eNOS-/- mice. Expression of NPR-A and NPR-C increased in the heart and tended to increase in the kidney of eNOS-/- mice. In the renal medulla in particular, increased expression of NPR-C was more prominent. Expression of TonEBP mRNA was markedly decreased in the renal medulla, but not in the renal cortex. Maximum binding capacity (B(max)) of ANP and C-ANP increased in the renal medulla in eNOS-/- mice.

CONCLUSION

These results suggest that the eNOS-NO system may be partly involved in regulation of ANP, NPR-A, -C, and TonEBP mRNA expression in the kidney.