Contributions of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery

1997 ◽  
Vol 273 (5) ◽  
pp. H2388-H2395 ◽  
Author(s):  
J. K. Shoemaker ◽  
J. R. Halliwill ◽  
R. L. Hughson ◽  
M. J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Forearm Blood Flow ◽  
Brachial Artery Diameter ◽  
Cholinergic Mechanism ◽  
Pulsed Doppler Ultrasound ◽  
Exercise Onset ◽  
Drug Treatments

The contributions of acetylcholine and/or nitric oxide (NO) to the rapid changes in human forearm blood flow (FBF) at the onset and recovery from mild exercise were studied in eight subjects. Rhythmic handgrip contractions were performed during brachial artery infusions of saline (2 ml/min; control), atropine (0.2 mg over 3 min), to block acetylcholine binding to muscarinic receptors, or atropine + N G-monomethyl-l-arginine (l-NMMA; 4 mg/min for 4 min), to additionally inhibit NO synthase. Brachial artery mean blood velocity (MBV; pulsed Doppler ultrasound) and diameter (echo Doppler) were measured continuously, and FBF was calculated. Atropine reduced acetylcholine-induced increases in FBF by ∼71% ( P < 0.05). FBF at rest was reduced by atropine and further reduced with atropine +l-NMMA. Both drug conditions reduced FBF during exercise by ∼10% compared with control, with no difference between drug treatments. Brachial artery diameter was unchanged from rest by exercise, recovery, and drug treatments. Neither drug treatment altered the rate or magnitude of the increase in FBF above rest. Peak FBF after exercise was reduced by atropine and atropine + l-NMMA. Total FBF during 5 min of recovery was reduced with atropine +l-NMMA compared with control and atropine. The results suggest that 1) acetylcholine and NO mechanisms additively contribute to FBF levels at rest, 2) a cholinergic mechanism adjusts the absolute FBF levels during exercise, 3) neither acetylcholine nor NO is essential to observe the normal time course or magnitude of the exercise response, and 4) NO contributes to the FBF response during recovery from exercise.

Effect of cardiac pacing on forearm vascular responses and nitric oxide function

2002 ◽  
Vol 283 (4) ◽  
pp. H1354-H1360 ◽  
Author(s):  
Daniel Green ◽  
Craig Cheetham ◽  
Chelsea Henderson ◽  
Rukshen Weerasooriya ◽  
Gerard O'Driscoll
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Blood Flow ◽  
Brachial Artery ◽  
Pulse Pressure ◽  
Forearm Blood Flow ◽  
Cardiac Pacing ◽  
Pulse Frequency ◽  
Brachial Artery Diameter

We examined the hypothesis that changes in heart rate at rest influence bioactivity of nitric oxide (NO) in humans by examining forearm blood flow responses during cardiac pacing in six subjects. Peak forearm and mean forearm blood flows across the cardiac cycle were continuously recorded at baseline and during pacing, with the use of high-resolution brachial artery ultrasound and Doppler flow velocity measurement. The brachial artery was cannulated to allow continuous infusion of saline or N G-monomethyl-l-arginine (l-NMMA). As heart rate increased, no changes in pulse pressure and mean or peak blood flow were evident. l-NMMA had no effect on brachial artery diameter, velocity, or flows compared with saline infusion. These results contrast with our recent findings that exercise involving the lower body, associated with increases in heart rate and pulse pressure, also increased forearm blood flow, the latter response being diminished by l-NMMA. These data suggest that changes in blood pressure, rather than pulse frequency, may be the stimulus for shear stress-mediated NO release in vivo.

Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans

1996 ◽  
Vol 81 (4) ◽  
pp. 1516-1521 ◽  
Author(s):  
J. K. Shoemaker ◽  
H. L. Naylor ◽  
Z. I. Pozeg ◽  
R. L. Hughson
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Forearm Blood Flow ◽  
Voluntary Contraction ◽  
Double Blind ◽  
Rate Of Increase ◽  
Forearm Exercise ◽  
Blind Manner ◽  
Exercise In Humans

Shoemaker, J. K., H. L. Naylor, Z. I. Pozeg, and R. L. Hughson. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans. J. Appl. Physiol. 81(4): 1516–1521, 1996.—The time course and magnitude of increases in brachial artery mean blood velocity (MBV; pulsed Doppler), diameter ( D; echo Doppler), mean perfusion pressure (MPP; Finapres), shear rate (γ˙ = 8 ⋅ MBV/ D), and forearm blood flow (FBF = MBV ⋅ π r 2) were assessed to investigate the effect that prostaglandins (PGs) have on the hyperemic response on going from rest to rhythmic exercise in humans. While supine, eight healthy men performed 5 min of dynamic handgrip exercise by alternately raising and lowering a 4.4-kg weight (∼10% maximal voluntary contraction) with a work-to-rest cycle of 1:1 (s/s). When the exercise was performed with the arm positioned below the heart, the rate of increase in MBV and γ˙ was faster compared with the same exercise performed above the heart. Ibuprofen (Ibu; 1,200 mg/day, to reduce PG-induced vasodilation) and placebo were administered orally for 2 days before two separate testing sessions in a double-blind manner. Resting heart rate was reduced in Ibu (52 ± 3 beats/min) compared with placebo (57 ± 3 beats/min) ( P < 0.05) without change to MPP. With placebo, D increased in both arm positions from ∼4.3 mm at rest to ∼4.5 mm at 5 min of exercise ( P < 0.05). This response was not altered with Ibu ( P > 0.05). Ibu did not alter the time course of MBV or forearm blood flow ( P > 0.05) in either arm position. The γ˙ was significantly greater in Ibu vs. placebo at 30 and 40 s of above the heart exercise and for all time points after 25 s of below the heart exercise ( P < 0.05). Because PG inhibition altered the time course ofγ˙ at the brachial artery, but not FBF, it was concluded that PGs are not essential in regulating the blood flow responses to dynamic exercise in humans.

Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation

2000 ◽  
Vol 99 (4) ◽  
pp. 261-267 ◽  
Author(s):  
Karen L. BERRY ◽  
R. Andrew P. SKYRME-JONES ◽  
Ian T. MEREDITH
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Arterial Occlusion ◽  
Flow Mediated Dilation ◽  
Reactive Hyperaemia ◽  
Upper Arm ◽  
Brachial Artery Diameter ◽  
Occlusion Cuff ◽  
Forearm Occlusion

Non-invasive ultrasound techniques to assess flow-mediated vasodilation (FMD) are frequently used to assess arterial endothelial vasodilator function. However, the range of normal values varies considerably, possibly due to differences in methodological factors. We sought to determine the effect of occlusion cuff position on the time course and magnitude of brachial artery blood flow and flow-mediated dilation. Twelve healthy subjects underwent measurements of forearm blood flow using venous occlusion plethysmography (VOP) before and after 5 min of susprasystolic cuff inflation, using two randomly assigned occlusion cuff positions (upper arm and forearm). An additional 16 subjects underwent two brachial ultrasound studies, using the two cuff positions, to assess the extent and time course of changes in brachial artery diameter and blood flow. Maximum increase in blood flow (peak reactive hyperaemia), measured by VOP, occurred immediately upon each cuff deflation, but was greater after upper arm compared with forearm arterial occlusion (33.1±3.1 versus 22.8±2.2 ml/min per forearm tissue, P = 0.001). Maximal brachial artery FMD was significantly greater following upper arm occlusion (9.0±1.2%, mean±S.E.M.) compared with forearm occlusion (5.9±0.7%, P = 0.01). The time course of the change in brachial artery diameter was affected differently in response to each protocol. The time to peak dilation following upper arm occlusion was delayed by 22 s compared with forearm occlusion. Occlusion cuff position is thus a powerful determinant of peak reactive hyperaemia, volume repaid and the extent and time course of brachial artery FMD. Positioning the cuff on the upper arm produces a greater FMD. These results highlight the need for comparisons between FMD studies to be made with care.

scholarly journals Phosphodiesterase-5 inhibition preserves exercise-onset vasodilator kinetics when NOS activity is reduced

2018 ◽  
Vol 124 (2) ◽  
pp. 276-282 ◽  
Author(s):  
J. Mikhail Kellawan ◽  
Jacqueline K. Limberg ◽  
Zachariah M. Scruggs ◽  
Wayne T. Nicholson ◽  
William G. Schrage ◽  
...  
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Time Course ◽  
Muscle Blood Flow ◽  
Rapid Onset ◽  
Guanosine Monophosphate ◽  
Moderate Intensity ◽  
Exercise Onset ◽  
No Bioavailability ◽  
Phosphodiesterase 5

Nitric oxide (NO)-mediated vasodilation contributes to the rapid rise in muscle blood flow at exercise onset. This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Whether PDE-5 limits exercise vasodilation onset kinetics is unknown. We hypothesized the time course of exercise vasodilation would be 1) accelerated during PDE-5 inhibition (sildenafil citrate, SDF) and 2) decelerated during NO synthase inhibition ( NG-monomethyl-l-arginine, l-NMMA), and 3) the effect of SDF on vasodilation onset kinetics would be attenuated with concurrent l-NMMA. Data from 29 healthy adults were analyzed. Individuals completed 5 min of moderate-intensity forearm exercise under control conditions and during 1) oral SDF ( n = 8), 2) intra-arterial l-NMMA ( n = 15), or 3) combined SDF + l-NMMA ( n = 6). Forearm blood flow (FBF; Doppler ultrasound of the brachial artery) and mean brachial artery blood pressure (MAP) were measured continuously. Forearm vascular conductance (FVC, FBF ÷ MAP) was curve-fit with a monoexponential model, and vasodilation onset kinetics were assessed by mean response time (MRT, time to achieve 63% of steady state). SDF had no effect on MRT ( P = 0.90). NOS inhibition increased MRT ( P = 0.01). MRT during SDF+l-NMMA was not different from control exercise ( P = 0.76). PDE-5 inhibition alone has no effect on rapid-onset vasodilation. Whereas NOS inhibition decelerates vasodilator kinetics, when combined with SDF, vasodilator kinetics do not differ from control. These data suggest NO-independent activation of cGMP occurs at exercise onset; thus PDE-5 inhibition may improve vasodilation in pathologies where NO bioavailability is impaired. NEW & NOTEWORTHY We show that when NO bioavailability is reduced, PDE-5 inhibition can restore vasodilation onset kinetics of exercise-mediated vasodilation via NO-independent cGMP pathways. These data suggest PDE-5 inhibition may improve exercise vasodilation onset kinetics in pathologies where NO bioavailability is impaired.

Effect of endothelin-1 on endothelium-derived vascular responsiveness in man

1998 ◽  
Vol 95 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Henry KRUM ◽  
Noel CRANSWICK ◽  
Anne-Marie PELLIZZER
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Blood Flow ◽  
Chronic Heart Failure ◽  
Brachial Artery ◽  
Forearm Blood Flow ◽  
Nitric Oxide Production ◽  
Reactive Hyperaemia ◽  
Endothelin 1 ◽  
Oxide Production

1.Endothelium-dependent vasodilatation via nitric oxide in response to muscarinic stimulation is decreased in chronic heart failure while basal release of nitric oxide may be increased. As production of the endothelium-derived vasoconstrictor endothelin-1 is increased in chronic heart failure, endothelin-1 may act in an autocrine manner to modulate these effects. 2.To test this, we determined whether prolonged endothelin infusion in normal subjects would reproduce the alterations in basal and stimulated nitric oxide release observed in patients with chronic heart failure. Basal nitric oxide production was determined by measurement of forearm blood flow using strain gauge venous occlusion plethysmography before and after brachial artery infusion of a nitric oxide synthase inhibitor (NG-monomethyl-l-arginine). Stimulated nitric oxide production was determined by brachial artery infusion of acetylcholine. As metabolic vasodilatation is thought to be mediated in part via nitric oxide and is decreased in chronic heart failure, forearm blood flow during peak reactive hyperaemia was also measured. Studies were then repeated during brachial artery infusion of endothelin-1 and a non-specific vasoconstrictor, noradrenaline. 3.Neither basal nor stimulated nitric oxide production was altered by endothelin-1 and noradrenaline infusion. However, absolute forearm blood flow responses to peak reactive hyperaemia were decreased during infusion of endothelin-1 in comparison to noradrenaline. These data suggest that increased endothelin-1 may not contribute greatly to altered basal and stimulated nitric oxide production in patients with chronic heart failure but may contribute to impaired metabolic vasodilatation, by mechanisms presumably unrelated to altered nitric oxide production.

scholarly journals Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction

1998 ◽  
Vol 85 (6) ◽  
pp. 2249-2254 ◽  
Author(s):  
R. W. Brock ◽  
M. E. Tschakovsky ◽  
J. K. Shoemaker ◽  
J. R. Halliwill ◽  
M. J. Joyner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Forearm Blood Flow ◽  
Mechanical Effect ◽  
Voluntary Contraction ◽  
Single Muscle ◽  
Cuff Inflation ◽  
S Period ◽  
Echo Doppler Ultrasound

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ∼20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with N G-monomethyl-l-arginine (l-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with l-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, butl-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereasl-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation thatl-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.

scholarly journals Contribution of adenosine to compensatory dilation in hypoperfused contracting human muscles is independent of nitric oxide

2011 ◽  
Vol 110 (5) ◽  
pp. 1181-1189 ◽  
Author(s):  
Darren P. Casey ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Steady State ◽  
Arterial Pressure ◽  
Brachial Artery ◽  
Adenosine Receptor ◽  
Receptor Blockade ◽  
Independent Manner ◽  
Control Value ◽  
Percent Recovery

We previously demonstrated that nitric oxide (NO) contributes to compensatory vasodilation in the contracting human forearm subjected to acute hypoperfusion. We examined the potential role of an adenosine-NO interaction to this response in 17 male subjects (25 ± 2 yr). In separate protocols subjects performed rhythmic forearm exercise (20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included exercise before inflation, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local [brachial artery catheter pressure (BAP)] and systemic [mean arterial pressure (MAP); Finometer] arterial pressure were measured. In protocol 1 ( n = 10), exercise was repeated during nitric oxide synthase inhibition [ NG-monomethyl-l-arginine (l-NMMA)] alone and during l-NMMA-aminophylline (adenosine receptor blockade) administration. In protocol 2, exercise was repeated during aminophylline alone and during aminophylline-l-NMMA. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from blood flow (ml/min) and BAP (mmHg). Percent recovery in FVC during inflation was calculated as (steady-state inflation + exercise value − nadir)/[steady-state exercise (control) value − nadir]. In protocol 1, percent recovery in FVC was 108 ± 8% during the control (no drug) trial. Percent recovery in FVC was attenuated with inhibition of NO formation alone (78 ± 9%; P < 0.01 vs. control) and was attenuated further with combined inhibition of NO and adenosine (58 ± 9%; P < 0.01 vs. l-NMMA). In protocol 2, percent recovery was reduced with adenosine receptor blockade (74 ± 11% vs. 113 ± 6%, P < 0.01) compared with control drug trials. Percent recovery in FVC was attenuated further with combined inhibition of adenosine and NO (48 ± 11%; P < 0.05 vs. aminophylline). Our data indicate that adenosine contributes to compensatory vasodilation in an NO-independent manner during exercise with acute hypoperfusion.

Dilator actions of arginine in human peripheral vasculature

1991 ◽  
Vol 81 (5) ◽  
pp. 695-700 ◽  
Author(s):  
Alison Calver ◽  
Joe Collier ◽  
Patrick Vallance
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Forearm Blood Flow ◽  
Hypotensive Effect ◽  
Linear Displacement ◽  
High Dose ◽  
Free Base ◽  
Peripheral Vasculature ◽  
Arginine Hydrochloride

1. l-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: d-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess l-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of l-and d-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects. 2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography. 3. In the superficial hand veins, l- and d-arginine free base and l- and d-arginine hydrochloride (all four preparations at a dose of 5 μmol/min) all caused a significant increase in venous diameter. The responses of the l-and d-enantiomers did not differ significantly from one another. 4. In the forearm resistance bed, l- and d-arginine free base and l-arginine hydrochloride were without effect at doses of 10 and 40 μmol/min. However, at doses of 160 μmol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another. 5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo. The response to arginine was not stereospecific: both the l- and d-enantiomers had the same effect. The dilator effect of high-dose arginine showed neither arterio-nor veno-selectivity. 6. This suggests that the hypotensive effect of systemic infusions of l-arginine in man is mediated by peripheral vasodilatation. It is not possible to ascribe the actions of arginine supplementation in this study to activation of the l-arginine/nitric oxide pathway through the provision of excess substrate.

Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation

2001 ◽  
Vol 280 (6) ◽  
pp. H2470-H2477 ◽  
Author(s):  
Julian P. J. Halcox ◽  
Suresh Narayanan ◽  
Laura Cramer-Joyce ◽  
Rita Mincemoyer ◽  
Arshed A. Quyyumi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Human Subjects ◽  
Epoxyeicosatrienoic Acid ◽  
Healthy Human ◽  
Human Forearm ◽  
Oxide Synthase ◽  
Cytochrome P 450

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography. Infusion of KCl (0.33 mmol/min) into the brachial artery caused baseline vasodilation and inhibited the vasodilator response to bradykinin, but not to sodium nitroprusside. Thus the incremental vasodilation induced by bradykinin was reduced from 14.3 ± 2 to 7.1 ± 2 ml · min−1 · 100 g−1( P < 0.001) after KCl infusion. A similar inhibition of the bradykinin ( P = 0.014), but not the sodium nitroprusside (not significant), response was observed with KCl after the study was repeated during preconstriction with phenylephrine to restore resting blood flow to basal values after KCl. Miconazole (0.125 mg/min) did not inhibit endothelium-dependent or -independent responses to ACh and sodium nitroprusside, respectively. However, after inhibition of cyclooxygenase and nitric oxide synthase with aspirin and N G-monomethyl-l-arginine, the forearm blood flow response to bradykinin ( P = 0.003), but not to sodium nitroprusside (not significant), was significantly suppressed by miconazole. Thus nitric oxide- and prostaglandin-independent, bradykinin-mediated forearm vasodilation is suppressed by high intravascular K+ concentrations, indicating a contribution of EDHF. In the human forearm microvasculature, EDHF appears to be a cytochrome P-450 derivative, possibly an epoxyeicosatrienoic acid.

scholarly journals Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound

2005 ◽  
Vol 98 (6) ◽  
pp. 2311-2315 ◽  
Author(s):  
Louise H. Naylor ◽  
Cara J. Weisbrod ◽  
Gerry O'Driscoll ◽  
Daniel J. Green
Keyword(s):  
Blood Flow ◽  
Brachial Artery ◽  
Peripheral Resistance ◽  
Artery Blood Flow ◽  
Brachial Artery Diameter ◽  
Resistance Vessel ◽  
Conduit Artery ◽  
Significant Difference ◽  
Vessel Structure

The purpose of this study was to establish valid indexes of conduit and resistance vessel structure in humans by using edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, to calculate conduit artery blood flow and diameter continuously across the cardiac cycle. Nine subjects aged 36.7 (9.2) yr underwent, on separate days, assessment of brachial artery blood flow and diameter response to 5-, 10-, and 15-min periods of forearm ischemia in the presence and absence of combined sublingual glyceryl trinitrate (GTN) administration. Two further sessions examined responses to ischemic exercise, one in combination with GTN. The peak brachial artery diameter was observed in response to the combination of ischemic exercise and GTN; a significant difference existed between resting brachial artery diameter and peak brachial artery diameter, indicating that resting diameter may be a poor measure of conduit vessel structure in vivo. Peak brachial artery flow was also observed in response to a combination of forearm ischemia exercise and GTN administration, the response being greater than that induced by periods of ischemia, GTN, or ischemic exercise alone. These data indicate that noninvasive indexes of conduit and resistance vessel structure can be simultaneously determined in vivo in response to a single, brief, stimulus and that caution should be applied in using resting arterial diameter as a surrogate measure of conduit artery structure in vivo.

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