Effect of chronic salt loading on adenosine metabolism and receptor expression in renal cortex and medulla in rats

Previous studies have shown that chronic salt loading increased renal inter stitial adenosine concentrations and desensitized renal effects of adenosin e, a phenomenon that could facilitate sodium excretion. However, the mechan isms responsible for the increased adenosine production and decreased adeno sine response are poorly understood. This study examined the effects of the dietary high salt intake on adenosine metabolism and receptor expression i n the renal cortex and medulla in Sprague Dawley rats. Fluorescent high-per formance liquid chromatography analyses were performed to determine adenosi ne levels in snap-frozen kidney tissues. Comparing rats fed a normal (1% Na Cl) versus high salt (4% NaCl) diet, renal adenosine concentrations in rats fed a high salt diet were significantly higher (cortex: 43+/-3 versus 85+/ -4, P<0.05; medulla: 183+/-4 versus 302+/-8 nmol/g wet tissue, P<0.05). Inc reased adenosine concentrations were not associated with changes in the 5'- nucleotidase or adenosine deaminase activity, as determined by quantitative isoelectric focusing and gel electrophoresis, Western blot analyses showed that a high salt diet (4% NaCl for 3 weeks) downregulated A(1) receptors ( antinatriuretic type), did not alter A(2A) and A(2B) receptors (natriuretic type), and upregulated A(3) receptors (function unknown) in both renal cor tex and medulla. The data show that stimulation of adenosine production and downregulation of A(1) receptors with salt loading may play an important r ole in adaptation in the kidney to promote sodium excretion.