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The article discusses the findings of a study which demonstrated how nitric oxide (NO) and prostaglandins (PG) contribute to increased blood flow during hypoxic exercise. The experiment involved 10 young healthy adults who were measured for forearm blood flow (FBF), and vascular conductance responses at moderate exercise intensity. The study concluded that NO and PG inhibition can reduce hypoxic exercise hyperaemia and eliminate hypoxic vasodilatation at rest.

Copyright of Journal of Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71% vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82% vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105% vs. 734 ± 126%) or SNP (1116 ± 111% vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not reduced with age in healthy humans. Further, our data also indicate that adenosine mediated vasodilatation is not reduced with age, and that ATP-mediated vasodilatation is independent of P1-receptor stimulation in both young and older adults. [ABSTRACT FROM AUTHOR]

Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance-trained adults. Accordingly, we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) SIT ( n= 12): six sessions of repeated (4–7) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days; (2) sedentary control ( n= 10); (3) single-bout SIT ( n= 9): one session of 4 × 30 s cycle ergometer sprints. Insulin sensitivity was determined (hyperinsulinaemic euglycaemic clamp) prior to and 72 h following each intervention. Compared with baseline, and sedentary and single-bout controls, SIT increased insulin sensitivity (glucose infusion rate: 6.3 ± 0.6 vs. 8.0 ± 0.8 mg kg−1 min−1; mean ±s.e.m.; P= 0.04). In a separate study, we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor (β-AR) stimulation, an important determinant of energy balance. Compared with baseline, and sedentary and single-bout control groups, SIT did not affect resting energy expenditure (EE: ventilated hood technique; 6274 ± 226 vs. 6079 ± 297 kJ day−1; P= 0.51) or the thermogenic response to isoproterenol (6, 12 and 24 ng (kg fat-free mass)−1 min−1: %ΔEE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P= 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial-derived factor, non-esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to β-AR stimulation. [ABSTRACT FROM AUTHOR]

Age-related increases in oxidative stress impair endothelium-dependent vasodilatation in humans, leading to the speculation that endothelial dysfunction contributes to impaired muscle blood flow and vascular control during exercise in older adults. We directly tested this hypothesis in 14 young (22 ± 1 years) and 14 healthy older men and women (65 ± 2 years). We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) responses to single muscle contractions at 10, 20 and 40% maximum voluntary contraction (MVC) before and during ascorbic acid (AA) infusion, and we also determined the effects of AA on muscle blood flow during mild (10% MVC) continuous rhythmic handgrip exercise. For single contractions, the peak rapid hyperaemic responses to all contraction intensities were impaired ∼45% in the older adults (all P < 0.05), and AA infusion did not impact the responses in either age group. For the rhythmic exercise trial, FBF (∼28%) and FVC (∼31%) were lower ( P= 0.06 and 0.05) in older versus young adults after 5 min of steady-state exercise with saline. Subsequently, AA was infused via brachial artery catheter for 10 min during continued exercise. AA administration did not significantly influence FBF or FVC in young adults (1–3%; P= 0.24–0.59), whereas FBF increased 34 ± 7% in older adults at end-exercise, and this was due to an increase in FVC (32 ± 7%; both P < 0.05). This increase in FBF and FVC during exercise in older adults was associated with improvements in vasodilator responses to acetylcholine (ACh; endothelium dependent) but not sodium nitroprusside (SNP; endothelium independent). AA had no effect on ACh or SNP responses in the young. We conclude that acute AA administration does not impact the observed age-related impairment in the rapid hyperaemic response to brief muscle contractions in humans; however, it does significantly increase muscle blood flow during continuous dynamic exercise in older adults, and this is probably due (in part) to an improvement in endothelium-dependent vasodilatation. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that adenosine triphosphate (ATP) can inhibit vasoconstrictor responses to endogenous noradrenaline release via tyramine in the skeletal muscle circulation, similar to what is observed in contracting muscle. Whether this involves direct modulation of postjunctional α-adrenoceptor responsiveness, or is selective for α1- or α2-receptors remains unclear. Therefore, in Protocol 1, we tested the hypothesis that exogenous ATP can blunt direct postjunctional α-adrenergic vasoconstriction in humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses to local intra-arterial infusions of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) during moderate rhythmic handgrip exercise (15% maximum voluntary contraction), during a control non-exercise vasodilator condition (adenosine), and during ATP infusion in eight young adults. Forearm hyperaemia was matched across all conditions. Forearm vasoconstrictor responses to direct α1-receptor stimulation were blunted during exercise versus adenosine (ΔFVC =−11 ± 3% versus−39 ± 5%; P< 0.05), and were abolished during ATP infusion (−3 ± 2%). Similarly, vasoconstrictor responses to α2-receptor stimulation were blunted during exercise versus adenosine (−13 ± 4% versus−40 ± 8%; P< 0.05), and were abolished during ATP infusion (−4 ± 4%). In Prototol 2 ( n= 10), we tested the hypothesis that graded increases in ATP would reduce α1-mediated vasoconstriction in a dose-dependent manner compared with vasodilatation evoked via adenosine. Forearm vasoconstrictor responses during low dose adenosine (−38 ± 3%) and ATP (−33 ± 2%) were not significantly different from rest (−40 ± 3%; P> 0.05). In contrast, vasoconstrictor responses during moderate (−22 ± 6%) and high dose ATP (−8 ± 5%) were significantly blunted compared with rest, whereas the responses during adenosine became progressively greater (moderate =−48 ± 4%, P= 0.10; high =−53 ± 6%, P< 0.05). We conclude that exogenous ATP is capable of blunting direct postjunctional α-adrenergic vasoconstriction, that this involves both α1- and α2-receptor subtypes, and that this is graded with ATP concentrations. Collectively, these data are consistent with the conceptual framework regarding how muscle blood flow and vascular tone are regulated in contracting muscles of humans. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that mechanical deformation of forearm blood vessels via acute increases in extravascular pressure elicits rapid vasodilatation in humans. In healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to whole forearm compressions and isometric muscle contractions with the arm above heart level. We used several experimental protocols to gain insight into how mechanical factors contribute to contraction-induced rapid vasodilatation. The findings from the present study clearly indicate that acute increases in extravascular pressure (200 mmHg for 2 s) elicit a significant rapid vasodilatation in the human forearm (peak ΔFVC∼155%). Brief, 6 s sustained compressions evoked the greatest vasodilatation (ΔFVC∼260%), whereas the responses to single (2 s) and repeated compressions (five repeated 2 s compressions) were not significantly different (ΔFVC∼155% versus∼115%, respectively). This mechanically induced vasodilatation peaks within 1–2 cardiac cycles, and thus is dissociated from the temporal pattern normally observed in response to brief muscle contractions (∼4–7 cardiac cycles). A non-linear relation was found between graded increases in extravascular pressure and both the immediate and peak rapid vasodilatory response, such that the responses increased sharply from 25 to 100 mmHg, with no significant further dilatation until 300 mmHg (maximal ΔFVC∼185%). This was in contrast to the linear intensity-dependent relation observed with muscle contractions. Our collective findings indicate that mechanical influences contribute largely to the immediate vasodilatation (first cardiac cycle) observed in response to a brief, single contraction. However, it is clear that there are additional mechanisms related to muscle activation that continue to cause and sustain vasodilatation for several more cardiac cycles after contraction. Additionally, the potential contribution of mechanical influences to the total contraction-induced hyperaemia appears greatest for low to moderate intensity single muscle contractions, and this contribution becomes less significant for sustained and repeated contractions. Nevertheless, this mechanically induced vasodilatation could serve as a feedforward mechanism to increase muscle blood flow at the onset of exercise, as well as in response to changes in contraction intensity, prior to alterations in local vasodilating substances that influence vascular tone. [ABSTRACT FROM AUTHOR]

Muscle sympathetic vasoconstrictor nerve activity increases with advancing age, but does not result in elevated forearm vasoconstrictor tone because of a selective reduction in α1-adrenoceptor responsiveness. In contrast, the leg circulation of older adults is under greater tonic sympathetic vasoconstriction, but it is unclear whether α-adrenoceptor responsiveness is altered with age. In the present study, we tested the hypothesis that postjunctional α-adrenergic vasoconstrictor responsiveness is reduced in the leg circulation with age. We measured femoral blood flow (Doppler ultrasound) and calculated the femoral vascular conductance (FVC) responses to α-adrenoceptor stimulation during local blockade of β-adrenoceptors in 12 young (24 ± 1 year) and seven healthy older men (62 ± 2 year). Whole-leg vasoconstrictor responses to local intrafemoral artery infusions of tyramine (evokes noradrenaline (NA) release), phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were assessed. Consistent with previous data, resting femoral blood flow and FVC were ∼30% lower in older compared with young men ( P < 0.05). Maximal vasoconstrictor responses to tyramine (−30 ± 3 versus−41 ± 3%), phenylephrine (−25 ± 4 versus−45 ± 5%), and dexmedetomidine (−22 ± 4 versus−44 ± 3%) were all significantly lower in older compared with young men (all P < 0.05). Our results indicate that human ageing is associated with a reduction in leg postjunctional α-adrenoceptor responsiveness to endogenous NA release, and this reduction is evident for both α1- and α2-adrenoceptors. However, given that basal leg vascular conductance is reduced with age and is primarily mediated by sympathetic vasoconstriction, impaired α-adrenoceptor responsiveness does not negate the ability of the sympathetic nervous system to evoke greater tonic vasoconstriction in the leg vasculature of older men. [ABSTRACT FROM AUTHOR]

Muscle sympathetic vasoconstrictor nerve activity increases with advancing age, but does not result in elevated forearm vasoconstrictor tone due to a selective reduction in α1-adrenergic receptor responsiveness. In contrast, the leg circulation of older adults is under greater tonic sympathetic vasoconstriction, but it is unclear whether leg α-receptor responsiveness is altered with age. We tested the hypothesis that α-adrenergic receptor responsiveness is not reduced in the leg circulation with age. In 12 young (24±1 yrs) and 7 healthy older men (62±2 yrs), we measured femoral blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses to alpha-adrenergic receptor stimulation via intra-femoral artery infusions of tyramine (evokes endogenous NE release), phenylephrine α1-agonist), and dexmedetomidine (α2-agonist) during local blockade of β-adrenergic receptors. At rest, femoral blood flow and vascular conductance were ∼30% lower in older compared with young men. Maximal vasoconstrictor responses (%ΔFVC) to tyramine (-30±3 vs -41±3%), phenylephrine (-25±4 vs -45±5%), and dexmedetomidine (-22±4 vs -44±3%) were significantly reduced in older compared with young men (all P<0.05). We conclude that aging is associated with impaired leg α-adrenergic receptor responsiveness at rest, and that this involves both α1- and α2-adrenergic receptors. [ABSTRACT FROM AUTHOR]