Effects of peripheral and spinal κ-opioid receptor stimulation on the exercise pressor reflex in decerebrate rats

Abstract

Copp SW, Stone AJ, Yamauchi K, Kaufman MP. Effects of peripheral and spinal -opioid receptor stimulation on the exercise pressor reflex in decerebrate rats. Am J Physiol Regul Integr Comp Physiol 307: R281-R289, 2014. First published June 11, 2014 doi:10.1152/ajpregu.00156.2014The exercise pressor reflex is greater in rats with ligated femoral arteries than it is in rats with freely perfused femoral arteries. The exaggerated reflex in rats with ligated arteries is attenuated by stimulation of -opioid and ␦-opioid receptors on the peripheral endings of thin-fiber muscle afferents. The effect of stimulation of -opioid receptors on the exercise pressor reflex is unknown. We tested the hypothesis that stimulation of -opioid receptors attenuates the exercise pressor reflex in rats with ligated, but not freely perfused, femoral arteries. The pressor responses to static contraction were compared before and after femoral arterial or intrathecal injection of the -opioid receptor agonist U62066 (1, 10, and 100 g). Femoral arterial injection of U62066 did not attenuate the pressor responses to contraction in either group of rats. Likewise, intrathecal injection of U62066 did not attenuate the pressor response to contraction in rats with freely perfused femoral arteries. In contrast, intrathecal injection of 10 and 100 g of U62066 attenuated the pressor response to contraction in rats with ligated femoral arteries, an effect that was blocked by prior intrathecal injection of the -opioid receptor antagonist nor-binaltorphimine. In rats with ligated femoral arteries, the pressor response to stimulation of peripheral chemoreceptors by sodium cyanide was not changed by intrathecal U62066 injections, indicating that these injections had no direct effect on the sympathetic outflow. We conclude that stimulation of spinal, but not peripheral, -opioid receptors attenuates the exaggerated exercise pressor reflex in rats with ligated femoral arteries. skeletal muscle afferents; exercise; peripheral artery disease; spiradoline ACTIVATION OF THE EXERCISE pressor reflex is responsible, at least in part, for the cardiovascular and ventilatory adjustments to exercise (13). The afferent arm of the reflex comprises group III and IV muscle afferents, which respond predominantly to mechanical and metabolic stimuli, respectively (14,19). Group III and IV afferents, which together are termed thin-fiber afferents, synapse onto interneurons in the dorsal horn of the spinal cord (10). These interneurons, in turn, project initially to neurons in the ventrolateral medulla and the nucleus of the solitary tract (9, 29), and eventually to autonomic preganglionic neurons. The functional consequences of activating the exercise pressor reflex during exercise include increases in arterial blood pressure, heart rate (HR), and ventilation, all of which contribute to the increases in exercising skeletal muscle blood flow and O 2 delivery (1, 2, 27).In cats, dogs, and rats, acute or chronic muscle ischemia exaggerates the exercise pressor reflex (8,19,27,32,3...

The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries

“…The incision was closed, and the rats were given 72 h to recover before any subsequent procedure. We did not perform any "sham" ligation procedures in this study because we have shown previously that a sham procedure does not result in an exaggerated pressor response to either static (11) or intermittent (10) hindlimb muscle contractions.…”

The exercise pressor reflex and peripheral artery disease

“…Contrary to findings concerning μ and δ receptors, stimulation of peripheral K-opioid receptors did not attenuate the exercise pressor reflex or mechanoreflex in either freely perfused or ligated rats. Stimulation of K-opioid receptors on the central endings of K-opioid receptors did, however, attenuate the exaggerated exercise pressor reflex in ligated rats (Copp et al, 2014). …”

Alteration of the mu opioid receptor: Ca2+channel signaling pathway in a subset of rat sensory neurons following chronic femoral artery occlusion

“…The DRG from freely perfused legs served as controls. We have shown recently that the pressor and cardioaccelerator responses to static contraction in sham-operated rats are not significantly different than those from rats with freely perfused sides (Copp et al 2014). Figure 9A shows the Western blots used for detecting MOR and G␣ i3 levels from four rats.…”