Endothelial processes contribute to vasoconstriction in acute renal failure (arf)

Intense renal vasoconstriction is a typical feature in such models of ARF as 1) the glycerol model of rhabdomyolysis and hemolysis, and 2) mercuric chloride (HgCh)To test the hypothesis that diminished arterial relaxation contributes to this vasoconstriction, we studied endothelial function by measuring contraction and relaxation of aortic rings in vitro. First, aortic rings dissected from control rats and from rats treated with IM glycerol (10 ml/kg bw) were contracted with phenylephrine (PE, 10^-7 M), and relaxation to vasodilators assessed. The relaxation to acetylcholinc (ACh 10^-6 M, expressed as % of PE contraction) was decreased significantly in the glycerol tissues (25%) as compared to control tissues (94%). In addition, the dose response curve for relaxation to nitroprusside was shifted to the right in the glycerol aortas. However, a cell pcrmeant form of cGMP was equally effective in relaxing the control and glycerol aortas. Second, we examined the effect of HgCl₂ (5 μM) applied in vitro for 20 minutes. HgCl₂-treated aortas relaxed less well to ACh than did control aortas (18 vs. 80%). In contrast to the glycerol model, nitroprusside was equally effective in relaxing HeCl₂-treated and control aortas. Because oxidant mechanisms cause injury in both models, we tested the capacity of the antioxidant pyruvate to prevent these effects of HgCl2- Pyruvate (5 mM) pre-trcatment preserved endothelial-dependent relaxation as assessed by ACh-mediated relaxation (HgCl₂, 30%; HgCL₂+ pyruvate, 73%). Conclusions: 1) Decreased endothelial-dependent relaxation occurs in the glycerol and HgChl₂ models. 2) In the glycerol model, effectiveness of both endothelial derived NO and exogenous NO donors is impeded, possibly due to scavenging of NO by heme proteins in the arterial wall. 3) In comparison, HgCfe impairs relaxation by toxic effects on the endothelium with attendant diminution in NO production. 4) In either model, the vascular smooth muscle function appears normal.