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ABSTRACT: Ligating the femoral artery for 72 hours in decerebrated rats exaggerates the exercise pressor reflex (EPR).The sensory arm of this reflex is comprised of group III and IV afferents, which can be either sensitized or stimulated by PGE2. In vitro studies showed that endoperoxide (EP) 3 and 4 receptors were responsible for the PGE2-induced sensitization of rat dorsal root ganglion cells. This in vitro finding prompted us to test the hypothesis that blockade of EP3 and / or EP4 receptors 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 femoral arterial injection of L798106 (an EP3 antagonist) or L161982 (an EP4 antagonist). 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 six ligated rats, however, the pressor response to contraction was attenuated by L161982, averaging 37 ± 3 mmHg before, 18 ± 2mmHg afterward (p < 0.05). Western blotting analysis revealed that ligation of the femoral artery for 72 hours increased the EP4 receptor protein in the L4 and L5 dorsal root ganglia over their freely perfused counterparts by 24% (p < 0.05). We conclude that EP4 receptors, but not EP3 receptors, play an important role in the exaggerated EPR found in rats with ligated femoral arteries.
The Journal of Physiology 04/2013; · 4.72 Impact Factor
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ABSTRACT: In decerebrated rats, we determined the dose of A803467, a NaV 1.8 antagonist, needed to attenuate the reflex pressor responses to femoral arterial injections of lactic acid (24mM; ∼0.1mL) and capsaicin (0.1μg), agents which stimulate thin fiber afferents having NaV 1.8 channels. We also determined whether the dose of A803467 needed to attenuate these reflex responses affected the responses of muscle spindle afferents to tendon stretch and succinylcholine (200μg). Spindle afferents are not supplied with NaV 1.8 channels, and consequently their responses to these stimuli should not be influenced by A803467. Pressor responses to lactic acid and capsaicin were not altered by 500μg of A803467 (n=6). A803467 in a dose of 1mg, however, significantly reduced (p< 0.05; n=12) the pressor responses to lactic acid (23±5 to 7±3ΔmmHg) and capsaicin (47±5 to 31±5ΔmmHg). Surprisingly, we also found that 1mg of A803467 reduced the responses of 10 spindle afferents to succinylcholine (34±11 to 4±3 Δ imp/s p<0.05) and stretch (83±17 to 0.4±1 Δ imp/s; p<0.05). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working on multiple channels, including NaV 1.8, other NaVs as well as voltage-gated calcium channels.
Neuroscience Letters 03/2013; · 2.11 Impact Factor
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ABSTRACT: We reported previously that tempol attenuated the exercise pressor and muscle mechanoreceptor reflexes in rats whose femoral arteries were ligated, whereas tempol did not attenuate these reflexes in rats whose femoral arteries were freely perfused. Although the mechanism whereby tempol attenuated these reflexes in rats whose femoral artery was ligated was independent of its ability to scavenge reactive oxygen species, its nature remains unclear. An alternative explanation for the tempol-induced attenuation of these reflexes involves ATP-sensitive potassium channels (K(ATP)) and calcium-activated potassium channels (BK(Ca)), both of which are opened by tempol. We tested the likelihood of this explanation by measuring the effects of either glibenclamide (0.1 mg/kg), which blocks K(ATP) channels, or iberiotoxin (20 or 40 μg/kg), which blocks BK(Ca) channels, on the tempol-induced attenuation of the exercise pressor and muscle mechanoreceptor reflexes in decerebrated rats whose femoral arteries were ligated. We found that glibenclamide prevented the tempol-induced attenuation of both reflexes, whereas iberiotoxin did not. We also found that the amount of protein comprising the pore of the K(ATP) channel in the dorsal root ganglia innervating hindlimbs whose femoral artery was ligated was significantly greater than that in the dorsal root ganglia innervating hindlimbs whose femoral arteries were freely perfused. In contrast, the amounts of protein comprising the BK(Ca) channel in the dorsal root ganglia innervating the ligated and freely perfused hindlimbs were not different. We conclude that tempol attenuated both reflexes by opening K(ATP) channels, an effect that hyperpolarized muscle afferents stimulated by static contraction or tendon stretch.
AJP Heart and Circulatory Physiology 05/2012; 303(3):H332-40. · 3.71 Impact Factor
