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 tes t whether isoproterenol has a similar effect on tubular replication in vitro. BALB/c mice were intraperitoneally injected with two different doses of isoproterenol in the presence or absence of the beta(1 + 2)- receptor antagonist propranolol. Proliferation of renal cells was eval uated by staining of tissue sections for proliferating cell nuclear an tigen (PCNA). In addition, cDNA amplification for PCNA was performed i n reverse-transcribed RNA isolated from renal cortex. Treatment of mic e with 0.1 mg/g body weight isoproterenol for 24 h significantly incre ased PCNA staining of nuclei compared to controls. This response was c ompletely blocked by propranolol. There was no light-microscopic evide nce that the proliferative response was subsequent to ischaemia with t ubular necrosis. Semiquantitative cDNA amplification revealed that iso proterenol also stimulated the RNA expression of the PCNA gene. This s tudy shows far the first time that isoproterenol directly stimulates p roliferation of mainly proximal tubular cells in vivo as detected by P CNA expression. Since proliferation and differentiation of tubular cel ls is pivotal for the recovery of renal function in many pathophysiolo gical situations, beta-adrenergic-mediated mitogenesis may be importan t in the reparative processes surrounding tubular epithelium regenerat ion.