Exercise prevents age-related decline in nitric-oxide-mediated vasodilator function in cutaneous microvessels

• Published in: The Journal of physiology Vol. 586; no. 14; pp. 3511 - 3524
• Main Authors: Black, Mark A., Green, Daniel J., Cable, N. Timothy
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 15.07.2008; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Adult; Aging - physiology; Capillaries - physiology; Cardiovascular; Dose-Response Relationship, Drug; Exercise - physiology; Female; Hot Temperature; Humans; Male; Middle Aged; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Skin - blood supply; Time Factors; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2008.153742

Ageing is associated with impaired endothelium-derived nitric oxide (NO) function in human microvessels. We investigated the impact of cardiorespiratory fitness and exercise training on physiological and pharmacological NO-mediated microvascular responses in older subjects. NO-mediated vasodilatation was examined in young, older sedentary and older fit subjects who had two microdialysis fibres embedded into the skin on the ventral aspect of the forearm and laser Doppler probes placed over these sites. Both sites were then heated to 42°C, with Ringer solution infused in one probe and N -nitro- l -arginine methyl ester ( l -NAME) through the second. In another study, three doses of ACh were infused in the presence or absence of l -NAME in similar subjects. The older sedentary subjects then undertook exercise training, with repeat studies at 12 and 24 weeks. The NO component of the heat-induced rise in cutaneous vascular conductance (CVC) was diminished in the older sedentary subjects after 30 min of prolonged heating at 42°C (26.9 ± 3.9%CVC max ), compared to older fit (46.2 ± 7.0%CVC max , P < 0.05) and young subjects (41.2 ± 5.2%CVC max , P < 0.05), whereas exercise training in the older sedentary group enhanced NO-vasodilator function in response to incremental heating ( P < 0.05). Similarly, the NO contribution to ACh responses was impaired in the older sedentary versus older fit subjects (low dose 3.2 ± 1.3 versus 6.6 ± 1.3%CVC max ; mid dose 11.4 ± 2.4 versus 21.6 ± 4.5%CVC max ; high dose 35.2 ± 6.0 versus 52.6 ± 7.9%CVC max , P < 0.05) and training reversed this (12 weeks: 13.7 ± 3.6, 28.9 ± 5.3, 56.1 ± 3.9%CVC max , P < 0.05). These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents age-related decline in indices of physiological and pharmacological microvascular NO-mediated vasodilator function. Since higher levels of NO confer anti-atherogenic benefit, this study has potential implications for the prevention of microvascular dysfunction in humans.