Comparison of forearm blood flow responses to incremental handgrip and cycle ergometer exercise: relative contribution of nitric oxide

The contribution of endothelium‐derived nitric oxide (NO) to exercise hyperaemia remains controversial. Disparate findings may, in part, be explained by different shear stress stimuli as a result of different types of exercise. We have directly compared forearm blood flow (FBF) responses to incremental handgrip and cycle ergometer exercise in 14 subjects (age ±s.e.m.) using a novel software system which calculates conduit artery blood flow continuously across the cardiac cycle by synchronising automated edge‐detection and wall tracking of high resolution B‐mode arterial ultrasound images and Doppler waveform envelope analysis. Monomethyl arginine (l‐NMMA) was infused during repeat bouts of each incremental exercise test to assess the contribution of NO to hyperaemic responses. During handgrip, mean FBF increased with workload (P < 0.01) whereas FBF decreased at lower cycle workloads (P < 0.05), before increasing at 120 W (P < 0.001). Differences in these patterns of mean FBF response to different exercise modalities were due to the influence of retrograde diastolic flow during cycling, which had a relatively larger impact on mean flows at lower workloads. Retrograde diastolic flow was negligible during handgrip. Although mean FBF was lower in response to cycling than handgrip exercise, the impact of l–NMMA was significant during the cycle modality only (P < 0.05), possibly reflecting the importance of an oscillatory antegrade/retrograde flow pattern on shear stress‐mediated release of NO from the endothelium. In conclusion, different types of exercise present different haemodynamic stimuli to the endothelium, which may result in differential effects of shear stress on the vasculature.

[1]  A. Dart,et al.  Four weeks of cycle training increases basal production of nitric oxide from the forearm. , 1997, The American journal of physiology.

[2]  D. Green,et al.  Effect of aerobic and resistance exercise training on vascular function in heart failure. , 2000, American journal of physiology. Heart and circulatory physiology.

[3]  M. Joyner,et al.  Role of nitric oxide in exercise hyperaemia during prolonged rhythmic handgripping in humans. , 1995, The Journal of physiology.

[4]  J. Coast Handbook of Physiology. Section 12. Exercise: Regulation and Integration of Multiple Systems , 1997 .

[5]  YukihitoHigashi,et al.  Regular Aerobic Exercise Augments Endothelium-Dependent Vascular Relaxation in Normotensive As Well As Hypertensive Subjects , 1999 .

[6]  Carter Vb,et al.  The power of words. , 1951, Lancet.

[7]  K. Chayama,et al.  Effect of Different Intensities of Exercise on Endothelium-Dependent Vasodilation in Humans: Role of Endothelium-Dependent Nitric Oxide and Oxidative Stress , 2003, Circulation.

[8]  S. Segal Integration of blood flow control to skeletal muscle: key role of feed arteries. , 2000, Acta physiologica Scandinavica.

[9]  B. Saltin,et al.  Muscle blood f low at onset of dynamic exercise in humans. , 1998, American journal of physiology. Heart and circulatory physiology.

[10]  S. Segal Communication Among Endothelial and Smooth Muscle Cells Coordinates Blood Flow Control During Exercise , 1992 .

[11]  J P Cooke,et al.  Cardiovascular effects of exercise: role of endothelial shear stress. , 1996, Journal of the American College of Cardiology.

[12]  N. Cable,et al.  Modification of forearm resistance vessels by exercise training in young men. , 1994, Journal of applied physiology.

[13]  R. Hughson,et al.  Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise. , 2003, Journal of applied physiology.

[14]  J. Wilson,et al.  Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans. , 1993, Journal of applied physiology.

[15]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.

[16]  M. Joyner,et al.  Local inhibition of nitric oxide and prostaglandins independently reduces forearm exercise hyperaemia in humans , 2004, The Journal of physiology.

[17]  G. Schuler,et al.  Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training. , 2001, Journal of the American College of Cardiology.

[18]  D. Green,et al.  Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide. , 2002, American journal of physiology. Heart and circulatory physiology.

[19]  A. Zeiher,et al.  Exercise and cardiovascular health: get active to "AKTivate" your endothelial nitric oxide synthase. , 2003, Circulation.

[20]  B. Blanksby,et al.  Endothelium-derived nitric oxide activity in forearm vessels of tennis players. , 1996, Journal of applied physiology.

[21]  G. Watts,et al.  Effects of exercise training on conduit and resistance vessel function in treated and untreated hypercholesterolaemic subjects. , 2003, European heart journal.

[22]  Hirofumi Tanaka,et al.  Regular Aerobic Exercise Prevents and Restores Age-Related Declines in Endothelium-Dependent Vasodilation in Healthy Men , 2000, Circulation.

[23]  A. Takeshita,et al.  Role of Nitric Oxide in Exercise‐Induced Vasodilation of the Forearm , 1994, Circulation.

[24]  G. New,et al.  Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation. , 1999, Cardiovascular research.

[25]  D. Green,et al.  Exercise training improves conduit vessel function in patients with coronary artery disease. , 2003, Journal of applied physiology.

[26]  P. Vanhoutte,et al.  Flow-induced release of endothelium-derived relaxing factor. , 1986, The American journal of physiology.

[27]  G. Kajiyama,et al.  Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. , 1999, Circulation.

[28]  P. Davies,et al.  Haemodynamic shear stress activates a K+ current in vascular endothelial cells , 1988, Nature.

[29]  D. Green,et al.  Exercise and the Nitric Oxide Vasodilator System , 2003, Sports medicine.

[30]  M. Joyner,et al.  From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs. , 2001, Journal of applied physiology.

[31]  G. Rådegran,et al.  Limb and skeletal muscle blood flow measurements at rest and during exercise in human subjects , 1999, Proceedings of the Nutrition Society.

[32]  Daniel Green,et al.  Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry. , 2002, Journal of applied physiology.

[33]  T. Griffith,et al.  Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. , 1991, The American journal of physiology.

[34]  J P Cooke,et al.  Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. , 1991, The Journal of clinical investigation.

[35]  D. Green,et al.  The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. , 2001, Journal of the American College of Cardiology.

[36]  B. Saltin,et al.  Nitric oxide in the regulation of vasomotor tone in human skeletal muscle. , 1999, American journal of physiology. Heart and circulatory physiology.

[37]  C. D. Nelson,et al.  Does autonomic blockade reveal a potent contribution of nitric oxide to locomotion-induced vasodilation? , 2000, American journal of physiology. Heart and circulatory physiology.

[38]  W. Franke,et al.  Effects of intense exercise training on endothelium-dependent exercise-induced vasodilatation. , 1998, Clinical physiology.

[39]  H. Krum,et al.  Exercise-induced vasodilation in forearm circulation of normal subjects and patients with congestive heart failure: role of endothelium-derived nitric oxide. , 1996, Journal of the American College of Cardiology.

[40]  G. Rådegran Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. , 1997, Journal of applied physiology.

[41]  J. M. Lash,et al.  Contribution of arterial feed vessels to skeletal muscle functional hyperemia. , 1994, Journal of applied physiology.

[42]  S. Moncada,et al.  EFFECTS OF ENDOTHELIUM-DERIVED NITRIC OXIDE ON PERIPHERAL ARTERIOLAR TONE IN MAN , 1989, The Lancet.

[43]  T Bull,et al.  Exercise training enhances endothelial function in young men. , 1996, Journal of the American College of Cardiology.

[44]  A. Quyyumi,et al.  Contribution of Endothelium‐Derived Nitric Oxide to Exercise‐Induced Vasodilation , 1994, Circulation.

[45]  G. New,et al.  Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm. , 1999, American journal of physiology. Heart and circulatory physiology.

[46]  T Togawa,et al.  Adaptive regulation of wall shear stress to flow change in the canine carotid artery. , 1980, The American journal of physiology.

[47]  T. Barstow,et al.  Effect of contraction frequency on leg blood flow during knee extension exercise in humans. , 2001, Journal of applied physiology.

[48]  L. Rowell Human Cardiovascular Control , 1993 .