PMID- 28295341 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20230804 IS - 1469-7793 (Electronic) IS - 0022-3751 (Print) IS - 0022-3751 (Linking) VI - 595 IP - 12 DP - 2017 Jun 15 TI - Exercise training reverses age-induced diastolic dysfunction and restores coronary microvascular function. PG - 3703-3719 LID - 10.1113/JP274172 [doi] AB - KEY POINTS: In a rat model of ageing that is free of atherosclerosis or hypertension, E/A, a diagnostic measure of diastolic filling, decreases, and isovolumic relaxation time increases, indicating that both active and passive ventricular relaxation are impaired with advancing age. Resting coronary blood flow and coronary functional hyperaemia are reduced with age, and endothelium-dependent vasodilatation declines with age in coronary resistance arterioles. Exercise training reverses age-induced declines in diastolic and coronary microvascular function. Thus, microvascular dysfunction and inadequate coronary perfusion are likely mechanisms of diastolic dysfunction in aged rats. Exercise training, initiated at an advanced age, reverses age-related diastolic and microvascular dysfunction; these data suggest that late-life exercise training can be implemented to improve coronary perfusion and diastolic function in the elderly. ABSTRACT: The risk for diastolic dysfunction increases with advancing age. Regular exercise training ameliorates age-related diastolic dysfunction; however, the underlying mechanisms have not been identified. We investigated whether (1) microvascular dysfunction contributes to the development of age-related diastolic dysfunction, and (2) initiation of late-life exercise training reverses age-related diastolic and microvascular dysfunction. Young and old rats underwent 10 weeks of exercise training or remained as sedentary, cage-controls. Isovolumic relaxation time (IVRT), early diastolic filling (E/A), myocardial performance index (MPI) and aortic stiffness (pulse wave velocity; PWV) were evaluated before and after exercise training or cage confinement. Coronary blood flow and vasodilatory responses of coronary arterioles were evaluated in all groups at the end of training. In aged sedentary rats, compared to young sedentary rats, a 42% increase in IVRT, a 64% decrease in E/A, and increased aortic stiffness (PWV: 6.36 +/- 0.47 vs.4.89 +/- 0.41, OSED vs. YSED, P < 0.05) was accompanied by impaired coronary blood flow at rest and during exercise. Endothelium-dependent vasodilatation was impaired in coronary arterioles from aged rats (maximal relaxation to bradykinin: 56.4 +/- 5.1% vs. 75.3 +/- 5.2%, OSED vs. YSED, P < 0.05). After exercise training, IVRT, a measure of active ventricular relaxation, did not differ between old and young rats. In old rats, exercise training reversed the reduction in E/A, reduced aortic stiffness, and eliminated impairment of coronary blood flow responses and endothelium-dependent vasodilatation. Thus, age-related diastolic and microvascular dysfunction are reversed by late-life exercise training. The restorative effect of exercise training on coronary microvascular function may result from improved endothelial function. CI - (c) 2017 The Authors. The Journal of Physiology (c) 2017 The Physiological Society. FAU - Hotta, Kazuki AU - Hotta K AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA. FAU - Chen, Bei AU - Chen B AD - Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA. FAU - Behnke, Bradley J AU - Behnke BJ AD - Department of Kinesiology & Johnson Cancer Research Center, Kansas State University, Manhattan, KS, USA. FAU - Ghosh, Payal AU - Ghosh P AD - Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA. FAU - Stabley, John N AU - Stabley JN AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Bramy, Jeremy A AU - Bramy JA AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA. FAU - Sepulveda, Jaime L AU - Sepulveda JL AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA. FAU - Delp, Michael D AU - Delp MD AD - Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL, USA. FAU - Muller-Delp, Judy M AU - Muller-Delp JM AUID- ORCID: 0000-0001-5322-0611 AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA. LA - eng GR - R01 HL077224/HL/NHLBI NIH HHS/United States GR - R01 HL090937/HL/NHLBI NIH HHS/United States GR - R21 AG044858/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170523 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 SB - IM CIN - J Physiol. 2017 Jul 15;595(14):4591-4592. PMID: 28466473 CIN - J Physiol. 2017 Jun 15;595(12):3701-3702. PMID: 28502077 CIN - J Physiol. 2017 Aug 1;595(15):5011-5012. PMID: 28590085 CIN - J Physiol. 2017 Sep 1;595(17):5755-5756. PMID: 28691755 MH - Animals MH - Coronary Vessels/*physiology MH - Diastole/*physiology MH - Endothelium, Vascular/physiology MH - Male MH - Microvessels/*physiology MH - Physical Conditioning, Animal/*physiology MH - Pulse Wave Analysis/methods MH - Rats MH - Rats, Inbred F344 MH - Regional Blood Flow/physiology MH - Vascular Stiffness/physiology MH - Vasodilation/physiology MH - Ventricular Dysfunction/*physiopathology PMC - PMC5471361 OTO - NOTNLM OT - E/A OT - aortic stiffness OT - coronary arterioles OT - endothelium OT - rat EDAT- 2017/03/16 06:00 MHDA- 2018/03/20 06:00 PMCR- 2018/06/15 CRDT- 2017/03/16 06:00 PHST- 2017/02/11 00:00 [received] PHST- 2017/02/20 00:00 [accepted] PHST- 2017/03/16 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2017/03/16 06:00 [entrez] PHST- 2018/06/15 00:00 [pmc-release] AID - TJP12327 [pii] AID - 10.1113/JP274172 [doi] PST - ppublish SO - J Physiol. 2017 Jun 15;595(12):3703-3719. doi: 10.1113/JP274172. Epub 2017 May 23.