Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb

Abstract

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ~40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min(-1)·100 g(-1) in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min(-1)·100 g(-1)) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min(-1)·100 g(-1)). During exercise, NE reduced exercising muscle BF by ~16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT (P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

Cardiovascular Adaptations to Exercise Training

“…This phenomenon, termed functional sympatholysis (351), is thought to allow adequate perfusion and oxygen delivery to the contracting fibers (379). In accordance, inhibition of α-adrenergic tone has been shown to disturb the distribution of blood flow and oxygen extraction in contracting skeletal muscle by increasing blood flow around especially inactive muscle fibers (174). The mechanisms underlying functional sympatholysis is thought to involve locally released substances that modulate the postreceptor effect of norepinephrine binding to α-receptors on the smooth muscle cells (379).…”

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

“…Likewise, it plays a crucial role in the regulation of vascular tone due to its ability to control at the same time both peripheral resistances and cardiac output [ 53 ]. Heart failure is a chronic clinical syndrome in which the heart is incapable of pumping a suffi cient supply of blood to meet the metabolic requirements of the body or requires elevated ventricular fi lling pressures to accomplish this goal.…”

The effect of nitric oxide synthase inhibition with and without inhibition of prostaglandins on blood flow in different human skeletal muscles

“…Additionally, a cannula was placed under local anaesthesia in the femoral artery for local drug infusions. Subjects were then moved to the PET scanner with the femoral region in the gantry and the right leg was positioned in an in-house designed leg exercise dynamometer (Heinonen et al 2007(Heinonen et al , 2010a(Heinonen et al , b, 2012c(Heinonen et al , 2013bRuotsalainen et al 1997). Subjects were laying supine both during resting and exercising measurements.…”