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

Abstract

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 O2 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 ΔFVC (% 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.

Figure 1. Schematic diagram of experimental protocol

Measurements were obtained at baseline and incremental exercise (10% and 20% of maximum) under normoxic and hypoxic conditions. Both normoxic and hypoxic trials were performed during control (saline) and l-NMMA infusions. ACh, acetylcholine.

Figure 2. Change (Δ) in forearm blood flow (FBF) and forearm vascular conductance (FVC) due to hypoxic exercise during saline (control) and l-NMMA administration

At 10% or 20% forearm exercise, NO synthase inhibition (l-NMMA) reduced forearm blood flow (A and C) and vascular conductance (B and D) compared to control (saline) during hypoxic exercise. ^†P < 0.05 vs. normoxia. *P < 0.05 vs. control (saline).

Figure 3. Impact of ageing on the compensatory vasodilator response (% change in ΔFVC compared to respective normoxic exercise condition) to hypoxic exercise

Older adults tended to have an attenuated compensatory vasodilator response at 10% MVC (P = 0. 1) during control saline trials, whereas at 20% MVC the compensatory vasodilatation was substantially lower with ageing. l-NMMA significantly reduced the compensatory vasodilatation in young adults at both exercise intensities. However, there was no difference in the compensatory vasodilatation between control and l-NMMA trails in the older adults. Data for young adults is from previously published work (Casey et al. 2010). *P < 0.05 vs. control (saline); †P < 0.05 vs. young group.

Figure 4. Vasodilator response to exogenous acetylcholine (ACh) during saline and l-NMMA administration in young and older adults

The change (Δ) in forearm vascular conductance (FVC) in response to increasing doses of ACh were not significantly different between young and older adults during the saline (P = 0. 5) or l-NMMA trials (P = 0.38). However, l-NMMA blunted the vasodilator responses (ΔFVC) to ACh at all three doses in the young adults. Data for young adults is from previously published work (Casey et al. 2010). *P < 0.01 vs. control (saline) for young adults.