Hypergravity upregulates renal inducible nitric oxide synthase expression and nitric oxide production.

Gun Yoon,Choong Sik Oh,Hyun-Soo Kim

doi:10.18632/oncotarget.9253

Abstract

Exposure to hypergravity severely decreases renal blood flow, potentially causing renal dysfunction. Nitric oxide (NO), which is endogenously synthesized by inducible NO synthase (iNOS), plays an important role in the regulation of renal function. The purpose of this study was to examine the effect of hypergravity exposure on the production of NO in kidneys. To determine whether hypergravity induces renal hypoxia and alters renal iNOS expression and NO production, mice were exposed to short-term hypergravity at +3Gz for 1 h. The time course of iNOS mRNA expression, hypoxia-inducible factor (HIF)-1α expression, and NO production was examined. Renal HIF-1α levels were significantly elevated immediately after centrifugation, and this increase was sustained for 3 h post-exposure. iNOS mRNA levels were also significantly increased immediately after exposure and were maintained during the reoxygenation period. Immunohistochemical staining for iNOS revealed that the cortical tubular epithelium exhibited moderate to strong cytoplasmic iNOS immunoreactivity immediately after hypergravity exposure and during the reoxygenation period. The time course of NO production was similar to that of iNOS expression. Our results suggest that both hypoxia and reoxygenation might be involved in the upregulation of HIF-1α in the kidneys of mice exposed to hypergravity. Significant increases in renocortical iNOS expression immediately after centrifugation and during the reoxygenation period suggest that iNOS expression induced by hypergravity exposure might play a protective role against hypoxia/reoxygenation injury in the renal cortex. Further investigations are necessary to clarify the role of iNOS and NO in kidneys exposed to hypergravity.

Highlights

The development of a new generation of combat aircrafts with extended flight capabilities raises the problem of protection of the crew members against visceral organ diseases due to sustained gravitational (G) force exposure [1]
Factors related to renal hypoxia will considerably influence renal function and fluid balance
We investigated the effect of exposure to hypergravity on the expression of hypoxiainducible factor (HIF)-1α and inducible NO synthase (iNOS) and the production of Nitric oxide (NO) in the kidneys of mice

Summary

Introduction

The development of a new generation of combat aircrafts with extended flight capabilities raises the problem of protection of the crew members against visceral organ diseases due to sustained gravitational (G) force exposure [1]. Exposure to high G force is conclusively known to be harmful to the human body during aviation activities [2]. With rapid developments in aviation technology, pilots are frequently exposed to hypergravity. High-performance aircrafts involve sustained and repeated exposure of the crew to high G force that may exceed the limit of physiological tolerance, possibly resulting in pilot incapacitation and subsequent loss of life. When it occurs repeatedly, may cause cumulative, adverse stress responses in the body [3]. The G force is a unique stress that principally results in impaired visceral blood flow when the inertial vector is in the head-to-foot direction (+Gz) [1, www.impactjournals.com/oncotarget

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