title: Physiological stress increases renal injury in eNOS-knockout mice.
abstract: African Americans have a fourfold greater likelihood of developing end-stage renal disease (ESRD) compared with Caucasians. It has been proposed that the increased prevalence may be explained by non-traditional factors such as environmental stress and psychosocial factors. In this study, we used infrequent running to exhaustion as a physiological stressor to mimic real life experiences, such walking up stairs when an elevator is malfunctioning or running to catch a bus, to study its effect on renal injury in a hypertensive mouse model (endothelial nitric oxide synthase-deficient mice; eNOS(-/-)). This model has previously been shown to have renal injury comparable to that observed in African Americans. The effect of physiological stress on renal injury was examined in the setting of low (0.12%), control (0.45%) and high (8%) dietary salt. Following bouts of physiological stress, eNOS(-/-) mice had significantly greater interstitial inflammation compared with unstressed eNOS(-/-) mice (two-way analysis of variance (2-ANOVA), Holm-Sidak; P<0.01). Interestingly, eNOS(-/-) mice on a high-salt diet had greater interstitial inflammation compared with similarly stressed eNOS(-/-) mice on a low- or control-salt diet (2-ANOVA, Holm-Sidak; P<0.03). These effects of stress were independent of systolic blood pressure (141±7, 143±4, and 158±8 vs. 141±4, 138±5, 150±4 mm Hg; end of study vs. baseline, respectively). There was no significant effect of stress or dietary salt on renal injury in control wild-type mice (eNOS(+)/(+)). These data demonstrate that physiological stress exacerbates the renal injury associated with hypertension and that high-salt compounds this effect of stress. These results provide support for the idea that psychosocial and environmental factors contribute to the increased prevalence of ESRD in hypertensive African Americans.
authors.affiliation: Department of Biology, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA. mpointer@nccu.edu
authors.forename: Mildred A
authors.initials: MA
authors.lastname: Pointer
authors.forename: Geraldine
authors.initials: G
authors.lastname: Daumerie
authors.forename: LaKessha
authors.initials: L
authors.lastname: Bridges
authors.forename: Sadiqa
authors.initials: S
authors.lastname: Yancey
authors.forename: Kelly
authors.initials: K
authors.lastname: Howard
authors.forename: Wendell
authors.initials: W
authors.lastname: Davis
authors.forename: Paul
authors.initials: P
authors.lastname: Huang
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000150:complications; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000201:enzymology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D017673:Sodium Chloride, Dietary; D052250:Nitric Oxide Synthase Type III