Protective effect of prostacyclin on postischemic acute renal failure in the rat

Abstract

Infusion of prostacyclin (PGI2) reportedly attenuates renal ischemic injury in the dog and the rat. In the dog, PGI2 is a potent renal vasodilator; in the rat a direct action on the renal vasculature is not always apparent. To determine whether or not the protective effect of PGI2 on postischemic ARF was hemodynamically mediated, studies were performed in uninephrectomized Sprague-Dawley rats before and after a 40 minute period of complete renal artery occlusion. In response to the preischemic infusion of PGI2 for 30 minutes at 160 ng/kg body wt/min i.v. (N = 7), MAP and RBF fell to 86 ± 7% (P<0.0001) and 84 ± 9% (P<0.05) of baseline values, respectively. RVR initially declined to 81 ± 9% of baseline values (P<0.025) but returned to 102 ± 13% of baseline values prior to the period of ischemia. Following the period of ischemia, reflow of blood in the rats receiving PGI2 was delayed when compared to rats not receiving PGI2 (N = 7). RBF returned to only 76 ± 19% of the initial values in PGI2-treated rats (P<0.01) but to 90 ± 12% of the initial values in rats receiving buffer alone (NS). Observations made during the ensuing 48 hours in animals treated with either 80 (N = 8) or 160 ng/kg/body wt/min (N = 7) for 30 minutes before and four hours after the period of ischemia indicated that renal function improved to a greater extent in the PGI2-treated animals than in buffer-treated animals (N = 15) as judged by significantly-greater mean values of V, U(Osm), U(Cr) and C(Cr). On the second day after ischemia, C(In) was significantly greater in PGI2-treated animals than in the postischemic animals receiving buffer alone (77 ± 45 vs. 33 ± 20 μl/min/100 g body wt; P<0.05) despite the fact that no differences were found in the mean values of RBF (3.59 ± 1.08 vs. 3.43 ± 0.32 ml/min/100 g body wt.). Blinded analysis of the histological sections revealed significantly less evidence of tubular epithelial cell necrosis in the PGI2-treated animals (P<0.005). The data indicate that the protective effect of PGI2 on the renal response to ischemic injury in the Sprague-Dawley rat is not related to changes in RBF or RVR. Instead, the beneficial effect of PGI2 may be a result of cytoprotective properties as has been demonstrated in other tissues.