Isoproterenol stimulates tubular DNA replication in mice

The beta-adrenergic stimulant isoproterenol is a mitogen for cultured murine proximal tubular cells. The present study was undertaken to test whether isoproterenol has a similar effect on tubular replication in vivo. BALB/c mice were intraperitoneally injected with two different doses of isoproterenol in the presence or absence of beta 1 + 2-receptor antagonist propranolol. Proliferation of renal cells was evaluated by staining of tissue sections for proliferating cell nuclear antigen (PCNA). In addition, cDNA amplification for PCNA was performed in reverse-transcribed RNA isolated from renal cortex. Treatment of mice with 0.1 mg/g body weight isoproterenol for 24 h significantly increased PCNA staining of nuclei compared to controls. This response was completely blocked by propranolol. There was no light-microscopic evidence that the proliferative response was subsequent to ischaemia with tubular necrosis. Semiquantitative cDNA amplification revealed that isoproterenol also stimulated the RNA expression of the PCNA gene. This study shows for the first time that isoproterenol directly stimulates proliferation of mainly proximal tubular cells in vivo as detected by PCNA expression. Since proliferation and differentiation of tubular cells is pivotal for the recovery of renal function in many pathophysiological situations, beta-adrenergic-mediated mitogenesis may be important in the reparative processes surrounding tubular epithelium regeneration.