Abstract
Oxygen delivery to skeletal muscle is regulated precisely to match the oxygen demand;
however, with aging the regulation of oxygen delivery during exercise is impaired. The present
thesis investigated mechanisms underlying the age-related impairment in regulation of blood
flow and oxygen delivery to contracting skeletal muscle. Two studies, one acute exercise study
and one large 8-week training intervention study, were conducted in young (18-28 years) and
older (65-80 years) healthy, male subjects. In both studies, pharmacologic potentiation of the
formation of cyclic guanosine monophosphate (cGMP) was used as intervention, and skeletal
muscle blood flow, oxygen delivery, and functional sympatholysis was examined.
The two studies included 53 healthy, habitually active, male subjects. All subjects participated
in an experimental day in which femoral arterial blood flow and blood pressure were assessed
and blood sampling were obtained. A total of 30 subjects (15 young and 15 older) participated
in the training intervention study and were tested before and after a period of high-intensity
interval training. In the acute exercise study and at baseline in the training intervention study,
it was demonstrated that potentiation of cGMP signaling increased leg blood flow, leg vascular
conductance and leg oxygen uptake during exercise in the older subjects but not in the young.
Interestingly, 8 weeks of exercise training abolished this effect of cGMP potentiation in the
older subjects. Collectively, this suggest that reduced cGMP signaling contribute to the impaired
skeletal muscle blood flow and oxygen delivery in older men and that an enhancement in cGMP
signaling is one of the mechanisms underlying the training-induced improvement in the
regulation of blood flow and oxygen delivery during exercise in older men.
In order to elucidate if an improved functional sympatholysis contributed to the increased leg
blood flow in the older subjects with cGMP potentiation, leg vascular conductance was assessed
during exercise with simultaneous femoral infusion of tyramine. No difference was observed
between the tyramine-evoked attenuation of vascular conductance in the control situation and
with cGMP potentiation; hence, cGMP potentiation was not associated with an improved
functional sympatholysis. It was also shown that exercise training improved functional
sympatholysis in the young but not in the older subjects, which suggest that improving
sympatholytic capacity by training may be a slower process in older than in young men.
In conclusion, this thesis provides new important knowledge related to the regulation of
skeletal muscle blood flow in aging. Specifically, it demonstrates that changes in cGMP signaling
is an underlying cause of age-related impairments in vascular function but also one of the
mechanisms underlying exercise training-induced vascular improvements. Future studies
should evaluate to what extent cGMP signaling is central in diseases with impaired blood flow
and exercise intolerance, such as diabetes.
however, with aging the regulation of oxygen delivery during exercise is impaired. The present
thesis investigated mechanisms underlying the age-related impairment in regulation of blood
flow and oxygen delivery to contracting skeletal muscle. Two studies, one acute exercise study
and one large 8-week training intervention study, were conducted in young (18-28 years) and
older (65-80 years) healthy, male subjects. In both studies, pharmacologic potentiation of the
formation of cyclic guanosine monophosphate (cGMP) was used as intervention, and skeletal
muscle blood flow, oxygen delivery, and functional sympatholysis was examined.
The two studies included 53 healthy, habitually active, male subjects. All subjects participated
in an experimental day in which femoral arterial blood flow and blood pressure were assessed
and blood sampling were obtained. A total of 30 subjects (15 young and 15 older) participated
in the training intervention study and were tested before and after a period of high-intensity
interval training. In the acute exercise study and at baseline in the training intervention study,
it was demonstrated that potentiation of cGMP signaling increased leg blood flow, leg vascular
conductance and leg oxygen uptake during exercise in the older subjects but not in the young.
Interestingly, 8 weeks of exercise training abolished this effect of cGMP potentiation in the
older subjects. Collectively, this suggest that reduced cGMP signaling contribute to the impaired
skeletal muscle blood flow and oxygen delivery in older men and that an enhancement in cGMP
signaling is one of the mechanisms underlying the training-induced improvement in the
regulation of blood flow and oxygen delivery during exercise in older men.
In order to elucidate if an improved functional sympatholysis contributed to the increased leg
blood flow in the older subjects with cGMP potentiation, leg vascular conductance was assessed
during exercise with simultaneous femoral infusion of tyramine. No difference was observed
between the tyramine-evoked attenuation of vascular conductance in the control situation and
with cGMP potentiation; hence, cGMP potentiation was not associated with an improved
functional sympatholysis. It was also shown that exercise training improved functional
sympatholysis in the young but not in the older subjects, which suggest that improving
sympatholytic capacity by training may be a slower process in older than in young men.
In conclusion, this thesis provides new important knowledge related to the regulation of
skeletal muscle blood flow in aging. Specifically, it demonstrates that changes in cGMP signaling
is an underlying cause of age-related impairments in vascular function but also one of the
mechanisms underlying exercise training-induced vascular improvements. Future studies
should evaluate to what extent cGMP signaling is central in diseases with impaired blood flow
and exercise intolerance, such as diabetes.
| Originalsprog | Engelsk |
|---|
| Udgivelsessted | Copenhagen |
|---|---|
| Forlag | Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen |
| Antal sider | 59 |
| ISBN (Trykt) | 978-87-7209-015-1 |
| Status | Udgivet - 2017 |
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