Functional sympatholysis is impaired in hypertensive humans

Non‐technical summary  In healthy individuals, blunting of the vasoconstriction caused by activation of the sympathetic nervous system is thought to be an important mechanism that optimizes blood flow to the working muscles. We show for the first time that this protective mechanism, called functional sympatholysis, is impaired in middle‐aged patients with high blood pressure. We also show that this impairment can be reversed by treatment with an angiotensin receptor blocker, but not with a thiazide‐type diuretic. These findings indicate that angiotensin II may augment sympathetic vasoconstriction in the active muscles of hypertensive humans, which may explain the exaggerated rise in blood pressure and blunted decline in systemic vascular resistance during exercise in this population.

[1]  W. Rose,et al.  Exaggerated sympathetic and pressor responses to handgrip exercise in older hypertensive humans: role of the muscle metaboreflex. , 2010, American journal of physiology. Heart and circulatory physiology.

[2]  R. Victor,et al.  Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug. , 2008, The American journal of medicine.

[3]  B. Parker,et al.  Evidence for reduced sympatholysis in leg resistance vasculature of healthy older women. , 2007, American journal of physiology. Heart and circulatory physiology.

[4]  M. Garry,et al.  Exercise pressor reflex function is altered in spontaneously hypertensive rats , 2006, The Journal of physiology.

[5]  J. Shelton,et al.  Reactive Oxygen Species Impair Sympathetic Vasoregulation in Skeletal Muscle in Angiotensin II–Dependent Hypertension , 2006, Hypertension.

[6]  M. Rondon,et al.  Abnormal muscle metaboreflex control of sympathetic activity in never-treated hypertensive subjects. , 2006, American journal of hypertension.

[7]  H. Krum,et al.  Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension. , 2006, American journal of physiology. Heart and circulatory physiology.

[8]  M. Joyner,et al.  Impaired modulation of sympathetic α‐adrenergic vasoconstriction in contracting forearm muscle of ageing men , 2005, The Journal of physiology.

[9]  V. Dzau.  The cardiovascular continuum and renin–angiotensin–aldosterone system blockade , 2005, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[10]  B. Levine,et al.  Persistent Sympathetic Activation During Chronic Antihypertensive Therapy: A Potential Mechanism for Long Term Morbidity? , 2005, Hypertension.

[11]  P. Fadel,et al.  Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy , 2004, The Journal of physiology.

[12]  B. Folkow.  Pathogenesis of structural vascular changes in hypertension. , 2004, Journal of hypertension.

[13]  J. Morrow,et al.  Angiotensin receptor blockade improves arterial distensibility and reduces exercise-induced pressor responses in obese hypertensive patients with the metabolic syndrome. , 2004, American journal of hypertension.

[14]  P. Raven,et al.  Inhibition of α‐adrenergic vasoconstriction in exercising human thigh muscles , 2004 .

[15]  D. Proctor,et al.  Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation , 2003, The Journal of physiology.

[16]  M. Joyner,et al.  α1- and α2-adrenergic vasoconstriction is blunted in contracting human muscle , 2003 .

[17]  M. Esler.  Differentiation in the effects of the angiotensin II receptor blocker class on autonomic function. , 2002, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[18]  R. Victor,et al.  Nitric oxide‐dependent modulation of sympathetic neural control of oxygenation in exercising human skeletal muscle , 2002, The Journal of physiology.

[19]  R. Victor,et al.  Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions: Role of Oxidative Stress , 2001, Circulation research.

[20]  P. Lund-johansen,et al.  Long-term central hemodynamic effects at rest and during exercise of losartan in essential hypertension. , 2000, American heart journal.

[21]  J Hansen,et al.  Metabolic modulation of sympathetic vasoconstriction in exercising skeletal muscle. , 2000, Acta physiologica Scandinavica.

[22]  R. Victor,et al.  Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle. , 1996, The Journal of clinical investigation.

[23]  P. Clarkson,et al.  Impaired Exercise Tolerance in Hypertensive Patients , 1996, Annals of Internal Medicine.

[24]  L Bolinger,et al.  Validation of near-infrared spectroscopy in humans. , 1994, Journal of applied physiology.

[25]  Y. Lacourciére,et al.  Comparative effects of quinapril, atenolol, and verapamil on blood pressure and forearm hemodynamics during handgrip exercise. , 1994, American journal of hypertension.

[26]  R. Victor,et al.  Muscle metaboreflex triggers parallel sympathetic activation in exercising and resting human skeletal muscle. , 1994, The American journal of physiology.

[27]  G. D. Thomas,et al.  Inhibition of alpha 2-adrenergic vasoconstriction during contraction of glycolytic, not oxidative, rat hindlimb muscle. , 1994, The American journal of physiology.

[28]  J. Faber,et al.  ANG II reverses selective inhibition of alpha 2-adrenoceptor sensitivity after in vitro isolation of arterioles. , 1993, The American journal of physiology.

[29]  R W Parkey,et al.  Finger-specific flexor recruitment in humans: depiction by exercise-enhanced MRI. , 1992, Journal of applied physiology.

[30]  P. McLaughlin,et al.  Impaired cardiopulmonary response to exercise in moderate hypertension. , 1992, The Canadian journal of cardiology.

[31]  P. Lund-johansen.  Twenty‐Year Follow‐up of Hemodynamics in Essential Hypertension During Rest and Exercise , 1991, Hypertension.

[32]  J. McGrath,et al.  Postjunctional α‐adrenoceptors in the rabbit isolated distal saphenous artery: indirect sensitivity to prazosin of responses to noradrenaline mediated via postjunctional α2‐adrenoceptors , 1991 .

[33]  R. Nadeau,et al.  Abnormal cardiovascular reactivity in borderline and mild essential hypertension. , 1991, Hypertension.

[34]  M. Blaha,et al.  Antihypertensive effect of isradipine on blood pressure at rest and during exercise. , 1991, American journal of hypertension.

[35]  J. McGrath,et al.  Influence of angiotensin II on the α‐adrenoceptors involved in mediating the response to sympathetic nerve stimulation in the rabbit isolated distal saphenous artery , 1991, British journal of pharmacology.

[36]  J. Staessen,et al.  Maximal aerobic power in essential hypertension. , 1988, Journal of hypertension.

[37]  R. Victor,et al.  Sympathetic nerve discharge is coupled to muscle cell pH during exercise in humans. , 1988, The Journal of clinical investigation.

[38]  Y. Shigematsu,et al.  Enhanced blood pressure response to isometric handgrip exercise in patients with essential hypertension: effects of propranolol and prazosin. , 1987, Journal of hypertension.

[39]  Phillips Mi.  Functions of Angiotensin in the Central Nervous System , 1987 .

[40]  M. Phillips.  Functions of angiotensin in the central nervous system. , 1987, Annual review of physiology.

[41]  S. Taylor,et al.  Influence of Nicardipine on the Blood Pressure at Rest and on the Pressor Responses to Cold, Isometric Exertion, and Dynamic Exercise in Hypertensive Patients , 1982, Journal of cardiovascular pharmacology.

[42]  A. Vallbo,et al.  Somatosensory, proprioceptive, and sympathetic activity in human peripheral nerves. , 1979, Physiological reviews.

[43]  Glezer Ga,et al.  Changes in general haemodynamics and renal function during exercise in patients with arterial hypertension. , 1975 .

[44]  G. Glezer,et al.  Changes in general haemodynamics and renal function during exercise in patients with arterial hypertension. , 1975, Cor et vasa.

[45]  J. Mitchell,et al.  Functional Sympatholysis During Muscular Activity: OBSERVATIONS ON INFLUENCE OF CAROTID SINUS ON OXYGEN UPTAKE , 1962, Circulation research.