Combination of Exercise Training and SOD Mimetic Tempol Enhances Upregulation of Nitric Oxide Synthase in the Kidney of Spontaneously Hypertensive Rats.

Pengyu Cao,Rong Rong,Osamu Ito,Daisuke Ito,Masahiro Kohzuki,Yang Zheng,Salvatore Corrao

doi:10.1155/2020/2142740

Abstract

Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.

Highlights

Exercise training (Ex) reduces the systemic blood pressure in human [1] and the hypertensive animal model including spontaneously hypertensive rats (SHR) [2, 3], Dahl saltsensitive rats [4], and angiotensin II-infused rats [5]
Effects of Ex and Tempol on Blood Pressure and Biochemical Variables in Plasma and Urine. e systolic blood pressure (SBP), DBP, body weight, kidney weight, and plasma variables in the four groups of SHR and Wistar–Kyoto rats (WKY) are shown in Tables 1–3. e SBP, DBP, triglyceride, glucose, renal and aorta NADPH oxidase activities, and plasma and urinary H2O2 and NOx were significantly higher in the control SHR group than in the control WKY group (P < 0.01), but plasma creatinine and urea nitrogen and creatinine clearance were not significantly different between these control groups
Ex increased the NO synthase (NOS) activity and protein levels of eNOS and nNOS in the aorta and kidney of SHR and WKY, the mechanism of the Ex-upregulated Nitric oxide (NO) system in the kidney has not yet been discovered

Summary

Introduction

Exercise training (Ex) reduces the systemic blood pressure in human [1] and the hypertensive animal model including spontaneously hypertensive rats (SHR) [2, 3], Dahl saltsensitive rats [4], and angiotensin II-infused rats [5]. Nitric oxide (NO) is a vasodilatory factor that can be synthesized by three isoforms of NO synthase (NOS): endothelial, neuronal, and inducible NOS (eNOS, nNOS, and iNOS), and it controls the systemic blood pressure and peripheral hemodynamics [9]. It has been reported that Ex increases the blood flow and NO production in the heart, aorta, and skeletal muscle [12, 13]. We recently reported that Ex increased NOS activity and expression levels of eNOS and nNOS in the aorta and kidney of SHR and normotensive Wistar–Kyoto rats (WKY) [14]

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Results

Conclusion