Endoperoxide 4 receptors attenuate the exercise pressor reflex in rats with ligated femoral arteries

Abstract

Ligating the femoral artery for 72 hours in in decerebrated rats exaggerates the exercise pressor response (EPR).The sensory arm of this reflex is comprised of group III and IV afferents, which can be either sensitized or stimulated by PGE2. Endoperoxide (EP) 3 and EP4 (PGE2 subtype) receptors were found to be responsible for the PGE2‐induced sensitization of rat dorsal root ganglion cells. We tested the hypothesis that L798106 (EP3 antagonist) or L161982 (EP4 antagonist) attenuated the exaggerated exercise pressor reflex in rats with ligated femoral arteries. We measured the cardiovascular responses to static hindlimb contraction or tendon stretch before and after iliac arterial injection of L798106 or L161982. The pressor and cardioaccelerator responses to either contraction or tendon stretch were not attenuated by L798106 in either the ligated or freely perfused rats. Likewise in five rats whose hindlimb muscles were freely perfused, the pressor and cardioaccelerator responses to either contraction or tendon stretch were not attenuated by L161982. In the five ligated rats, however, the pressor response to contraction was attenuated by L161982, averaging 37 ± 3 mmHg before, 18 ± 2mmHg afterward (p < 0.05). In addition, western blots revealed that ligation of the femoral artery for 72 hours increased the EP4 receptor protein in the L4 and L5 dorsal root ganglion by 24% (p < 0.05) over their freely perfused counterparts. We conclude that blockade of EP4 receptors, but not blockade of EP3 receptors, attenuated the EPR in rats with ligated femoral arteries.