METABOLISM OF CAMP TO ADENOSINE IN THE RENAL VASCULATURE

We recently demonstrated that cAMP added to the perfusate increased th e renal venous recovery of adenosine in the isolated rat kidney, an ef fect blocked by inhibition of ecto-phosphodiesterase and ecto-5'-nucle otidase. Although our previous study established the cAMP-adenosine pa thway, i.e., the conversion of cAMP to adenosine, as a viable metaboli c pathway within the kidney, that study did not determine whether conv ersion of arterial cAMP to adenosine recoverable in the venous effluen t occurred in the tubules versus nontubular sites. In the current stud y, we addressed this issue by determining the effects of blocking cAMP transport into the renal tubules with probenecid (0.1, 0.3 and 1 mM) on the increase in renal venous output of adenosine induced by adding cAMP (30 mu M) to the perfusate of isolated rat kidneys. Addition of c AMP to the perfusate caused a marked increase in renal venous secretio n of adenosine, an effect that was augmented, rather than inhibited, b y probenecid. To test the hypothesis that the renal vasculature suppor ts a cAMP-adenosine pathway, cultured rat preglomerular vascular smoot h muscle cells were incubated with cAMP (30 mu M) for 1 hr in the pres ence and absence of 3-isobutyl-1-methylxanthine (a phosphodiesterase i nhibitor). Incubation with cAMP increased extracellular adenosine leve ls 41-fold, and this effect was abolished by 3-isobutyl-1-methylxanthi ne. In a third experimental series, addition of cAMP (0.3, 1, 3, 10 an d 30 mu M) to the perfusate of isolated rat kidneys and mesenteric vas cular beds increased the renal venous, but not mesenteric venous, outp ut of AMP, adenosine and inosine. We conclude that the renal vasculatu re supports a cAMP-adenosine pathway, that administering cAMP into the renal artery and measuring adenosine in the venous effluent of the pe rfused rat kidney most likely monitors primarily the renal vascular cA MP-adenosine pathway and that the quantitative importance of the cAMP- adenosine pathway is not equivalent in all vascular compartments.