Antioxidant treatment reverts increased arterial basal tone and oxidative stress in nephrectomized (5/6) hypertensive rats

Abstract

Nonischemic 5/6 nephrectomized rat (NefR) is a model of chronic kidney disease. However, little is known about vascular dysfunction and its relation with hypertension in NefR. Aims. To evaluate possible alterations of endothelial function, NObioavailability, and basal tone in aorta from NefR and the role of oxidative stress. Sprague Dawley rats were divided into sham rats (SR), NefR, and NefR treated with tempol (NefR-T). Mean arterial pressure (MAP) and renal function were determined. In isolated aortic rings the following was measured: 1-endothelial function, 2-basal tone, 3-NO levels, 4-membrane potential (MP), and 5-oxidative stress. NefR increased MAP (SR: 119 ± 4 mmHg; 𝑛=7; NefR: 169 ± 6; 𝑛=8; 𝑃 < 0.001). Tempol did not modify MAP (NefR-T: 168 ± 10; 𝑛=6; 𝑃 < 0.001). NefR showed endothelial dysfunction, increased basal tone and decreased NO levels (SR: 32 ± 2 nA; 𝑛=7, NefR: 10 ± 2; 𝑛=8; 𝑃 < 0.001). In both in vitro and in vivo tempol improves basal tone, NO levels, and MP. Oxidative stress in NefR was reverted in NefR-T. We described, for the first time, that aorta from NefR presented increased basal tone related to endothelial dysfunction and decreased NO-bioavailability. The fact that tempol improves NO-contents and basal tone, without decrease MAP, indicates that oxidative stress could be implicated early and independently to hypertension, in the vascular alterations.