Ageing reduces the compensatory vasodilatation during hypoxic exercise: the role of nitric oxide

Non-technical summary In young healthy humans, the combination of exercise and hypoxia produces a compensatory vasodilatation to ensure the maintenance of oxygen to the active muscles. We have previously demonstrated that nitric oxide (NO) is a major factor responsible for the compensatory vasodilatation. In this paper we show that the compensatory vasodilator response to hypoxic exercise is attenuated in older adults due to less NO signalling. These findings provide important information on the impact of ageing and the role of NO in the regulation of skeletal muscle blood flow during conditions of reduced oxygen availability.We tested the hypotheses that (1) the compensatory vasodilatation in skeletal muscle during hypoxic exercise is attenuated in ageing humans and (2) local inhibition of nitric oxide (NO) synthesis in the forearm of ageing humans will have less impact on the compensatory dilatation during rhythmic exercise with hypoxia, due to a smaller compensatory dilator response. Eleven healthy older subjects (61 +/- 2 years) performed forearm exercise (10% and 20% of maximum) during saline infusion (control) and NO synthase inhibition (NG-monomethyl-l-arginine; l-NMMA) under normoxic and normocapnic hypoxic (80% arterial O-2 saturation) conditions. Forearm vascular conductance (FVC; ml min-1 (100 mmHg)-1) was calculated from forearm blood flow (ml min-1) and blood pressure (mmHg). To further examine the effects of ageing on the compensatory vasodilator response to hypoxic exercise we compared the difference in delta FVC (% change compared to respective normoxic exercise trial) between the older subjects (present study) and previously published data from an identical protocol in young subjects. During the control condition, the compensatory vasodilator response to hypoxia was similar between the old and young groups at 10% exercise (28 +/- 6% vs. 40 +/- 8%, P = 0.11) but attenuated at 20% exercise (14 +/- 4% vs. 31 +/- 6%, P < 0.05). l-NMMA during hypoxic exercise only blunted the compensatory vasodilator response in the young group (P < 0.05). Our data suggest that ageing reduces the compensatory vasodilator response to hypoxic exercise via blunted NO signalling.