Relation of adenosine to medullary injury in the perfused rat kidney

Abstract

In isolated perfused rat kidneys the medullary thick ascending limb (mTAL) is uniquely vulnerable to cellular injury produced by its hypoxic milieu and exacerbated by active transport. Endogenous inhibitors of transport might therefore be expected to reduce cell injury. We studied the possible role of adenosine in altering mTAL damage in isolated rat kidneys perfused for 60 min. When adenosine deaminase was added to the recirculating perfusate in 8 experiments, severe damage to mTAL cells adjacent to the inner medulla was significantly exacerbated to involve 89.4 +/- 3% of them as compared to 74.9 +/- 4.7% in 9 controls (p less than 0.025). Similar results were obtained when 6-nitrobenzylthioinosine, which inhibits adenosine efflux from hypoxic cells, was added to the perfusion (n = 5, p less than 0.025). The addition of the adenosine analogue R(-)-phenylisopropyladenosine [R(-)-PIA] conferred protection, so that now only 12.5 +/- 2.5% of deep mTAL cells exhibited severe morphological damage (n = 7, p less than 0.005). The protective effect of R(-)-PIA was minimized by 8-phenyltheophylline, which blocks adenosine receptors. The S(+)-isomer of PIA was significantly less potent than R(-)-PIA in protecting against hypoxic injury. These results suggest that endogenous adenosine may play a role in modifying the injurious effects of anoxia on medullary cells, by inhibiting active transport.