Local adenosine receptor blockade accentuates the sympathetic responses to fatiguing exercise

Abstract

The role adenosine plays in evoking the exercise pressor reflex in humans remains controversial. We hypothesized that localized forearm adenosine receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from the peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed before and after adenosine receptor blockade by local infusion of 40 mg aminophylline in saline via forearm Bier block (regional intravenous anesthesia). In the second experiment, the same amount of saline was infused via the Bier block. After aminophylline, the MSNA and blood pressure responses to fatiguing handgrip, PECO, and passive stretch (all P < 0.05) were significantly greater than during the control condition. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data suggest that adenosine receptor antagonism in the exercising muscles may accentuate sympathetic activation during fatiguing exercise.

The Role Played by Adenosine in Modulating Reflex Sympathetic and Pressor Responses Evoked by Stimulation of TRPV1 in Muscle Afferents

“…Adenosine is involved in the regulation of numerous important processes in human skeletal muscle during exercise, such as blood flow and local vasodilation in response to ischemia [31]. Aminophylline, a nonspecific adenosine receptor antagonist, has been used to block adenosine receptors in a previous study, suggesting that adenosine receptor antagonism in the exercising muscles accentuates muscle SNA during fatiguing exercise [16]. Nonetheless, the mechanisms responsible for accentuated SNA response seen after aminophylline remain unknown.…”

“…In addition, femoral artery injection of adenosine increases SNA and BP only if the purine is allowed to re-circulate to the systemic circulation [15]. In contrast, the muscle reflex evoked by handgrip exercise is accentuated by injection into the brachial artery of theophylline, an adenosine receptor antagonist [16]. Other studies reported that adenosine does not lead to increases in SNA and BP and to evoke the muscle reflex [17, 18].…”

A role for nitric oxide within the nucleus tractus solitarii in the development of muscle mechanoreflex dysfunction in hypertension

“…Although it is tempting to interpret findings elicited during passive stretch as being directly representative of mechanoreflex activity, conclusions must be tempered with this limitation in mind. It should be noted that ideologically similar passive stretching techniques have recently been used in humans to elucidate the muscle mechanoreflex contribution to cardiovascular control (Fisher et al 2005; Cui et al 2006, 2008 a , b , 2010; Drew et al 2008 a , b ; Momen et al 2008). Results from these studies have proved invaluable in extending the findings from animal investigation to humans.…”

Skeletal Muscle Signaling and the Heart Rate and Blood Pressure Response to Exercise

“…14 Interstitial potassium (K + ), 15,16 pH, lactate, and adenosine have been suggested to contribute to the exercise pressor reflex by stimulating and sensitizing group IV fiber afferents in skeletal muscle, 11 although their individual contributions remain controversial. 11,17,18 Recently, ATP has been suggested to stimulate group IV afferents, 19 and a role for ATP is supported by the tight coupling between interstitial ATP concentrations and exercise intensity 20 and the relation between interstitial ATP and norepinephrine (NE) concentrations during exercise. 21,22 This study investigated the role of the training status of skeletal muscles on cardiovascular responses to exercise.…”