title: Long-term treadmill training ameliorates endothelium-dependent vasorelaxation mediated by insulin and insulin-like growth factor-1 in hypertension.
abstract: Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.
authors.affiliation: Graduate Institute of Clinical Medical Science and.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medical Science and Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Department of Healthcare Administration, Asia University, Taichung, Taiwan;
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Department of Occupational Therapy, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan;
authors.forename: Chia-Ting
authors.initials: CT
authors.lastname: Su
authors.affiliation: Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; and.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Exercise Science, University of Taipei, Taipei, Taiwan yangailun@gmail.com alyang@utaipei.edu.tw.
authors.forename: Ai-Lun
authors.initials: AL
authors.lastname: Yang
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000502:physiology*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases
keywords: IGF-1; aorta; hypertension; insulin; treadmill training; vasorelaxation