Blockade of acid sensing ion channels attenuates the augmented exercise pressor reflex in rats with chronic femoral artery occlusion

Abstract

In decerebrated rats, we reported previously that the pressor reflex arising from a limb whose femoral artery was occluded for 72 h before contraction was significantly higher than the pressor reflex arising from a contralateral freely perfused limb. Moreover, increased levels of acid sensing ion channel 3 (ASIC3) on muscle afferent neurons have been shown in rats whose femoral artery was occluded for 24 to 72 hours. These findings prompted us to examine whether blockade of acid sensing ion channels, especially ASIC3, contributed to the augmented pressor reflex evoked by static contraction in rats with chronic femoral artery occlusion. We found that the pressor reflex arising from the limb whose femoral artery was occluded for 72 h before contraction (32 ± 5 mmHg, n=9) was significantly attenuated by a non-selective ASIC antagonist amiloride (15 ± 3 mmHg, n=9, P=0.01) injected into abdominal aorta (50 μg/kg). Intravenous injection of this dose of amiloride had no effect on the pressor reflex. Likewise, the selective ASIC3 antagonist, APETx2 (100μg/kg), significantly attenuated the pressor response to static contraction in rats whose femoral artery was occluded for 72h before the start of contraction (before: 37 ± 6 mmHg, after: 18 ± 4 mmHg, n=4, P=0.008). We conclude that ASICs on muscle afferents are responsible for the augmented pressor reflex seen in rats with chronic femoral arterial occlusion.