Effect of tempol on inward‐rectifier K+ channel regulation of afferent arteriolar tone in diabetic rat kidney

Abstract

We previously reported that inward‐rectifier K+ channels (Kir) contribute to the decreased afferent arteriolar tone that accompanies streptozotocin (STZ)‐induced diabetes in the rat. We hypothesized that the oxidative stress characteristic of diabetes underlies this phenomenon. Sham and STZ rats were chronically‐treated with tempol (SOD mimetic; 9 ± 1 mg/day) or left untreated for 27 days. The in vitro blood‐perfused juxtamedullary nephron technique was used to quantify afferent arteriolar lumen diameter responses to Kir blockade (10, 30, 100 μM Ba2+). In untreated animals, lumen diameter averaged 23.8 ± 1.4 µm in STZ and 18.6 ± 1.9 μm in Sham rats (P=0.05) and the concentration‐dependent response to Ba2+ was exaggerated in the STZ group (100 nM Ba2+: Sham δ = ‐2.0 ± 0.7 μm, STZ δ = ‐7.9 ± 1.4 μm; P<0.001). In tempol‐treated animals, baseline lumen diameter did not differ between Sham and STZ rats, averaging 21.4 ± 1.4 and 21.1 ± 1.6 μm, respectively. Moreover, the afferent arteriolar diameter response to Ba2+ was attenuated in tempol‐treated STZ rats (100 nM Ba2+: δ = ‐2.4 ± 1.3 μm; P<0.05 vs untreated STZ) and did not differ from either untreated or tempol‐treated Sham rats. Thus, tempol normalized baseline diameter and the response to Ba2+ in afferent arterioles from STZ rats. We conclude that oxidative stress plays a role in the Kir‐dependent tonic afferent arteriolar dilation that occurs during STZ‐induced diabetes.