Endoperoxide 4 receptors play a role in evoking the exercise pressor reflex in rats with simulated peripheral artery disease

Yamauchi, K.; Kim, Joyce; Stone, Audrey J.; Ruiz‐Velasco, Victor; Kaufman, Marc P.

doi:10.1113/jphysiol.2012.247973

Cited by 34 publications

(47 citation statements)

References 39 publications

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“…In particular, 72 h of femoral artery ligation elicited a higher BP response to static contraction compared with control conditions (i.e., freely perfused femoral artery), and this augmented pressor response was attenuated by daltroban, a thromboxane receptor antagonist (18). In another study, Yamauchi and colleagues (41) showed that 72 h of femoral artery ligation increased endoperoxidade 4 receptor (a receptor for PGE 2 ) protein in the dorsal root ganglia; blockade of these receptors lowered the exercise pressor reflex. More recently, it has been shown that ketorolac administered into the spinal cord attenuated the pressor response to static contraction in rats (37).…”

Section: Discussionmentioning

confidence: 96%

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Müller

Drew

Ross

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Muller MD, Drew RC, Ross AJ, Blaha CA, Cauffman AE, Kaufman MP, Sinoway LI. Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease. Am J Physiol Heart Circ Physiol 309: H523-H528, 2015. First published June 8, 2015 doi:10.1152/ajpheart.00267.2015.-Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex, but the metabolite(s) responsible for this augmented response is not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise. Seven PAD patients underwent 4 min of single-leg dynamic plantar flexion (30 contractions/min) in the supine posture (workload: 0.5-2.0 kg). MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Ketorolac did not affect MAP or HR at rest. During the first 20 s of exercise with the most symptomatic leg, ⌬MAP was significantly attenuated by ketorolac (2 Ϯ 2 mmHg) compared with control (8 Ϯ 2 mmHg, P ϭ 0.005), but ⌬HR was similar (6 Ϯ 2 vs. 5 Ϯ 1 beats/min). Importantly, patients rated the exercise bout as "very light" to "fairly light," and average pain ratings were 1 of 10. Ketorolac had no effect on perceived exertion or pain ratings. Ketorolac also had no effect on MAP or HR in seven age-and sex-matched healthy subjects who performed a similar but longer plantar flexion protocol (workload: 0.5-7.0 kg). These data suggest that prostanoids contribute to the augmented exercise pressor reflex in patients with PAD. PERIPHERAL ARTERIAL DISEASE (PAD) is a form of atherosclerosis that preferentially affects the lower extremity. Because leg blood flow is impaired in PAD, it is not surprising that dynamic exercise, such as walking, provokes pain in the calf, thigh, or buttocks, termed "intermittent claudication." Clinical exercise testing (e.g., the Bruce treadmill protocol) also causes a large increase in blood pressure (BP) in PAD patients, and studies (10, 11) have linked this augmented pressor response to cardiovascular morbidity and mortality. In recent years, our laboratory has focused on BP control in patients with PAD. Specifically, we found that 1) the BP response to single-leg dynamic plantar flexion exercise was augmented in PAD patients compared with healthy control subjects; 2) the pressor response occurred at very low workloads and before the onset of pain; 3) the pressor response correlated with the anklebrachial index (ABI), suggesting that disease severity plays a role; and 4) intravenous infusion of ascorbic acid lowered the pressor response to exercise in PAD (13,28). To date, the mechanisms for these findings are largely unknown. Understanding BP regulation during exercise in PAD ...

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Section: Discussionmentioning

confidence: 96%

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Müller

Drew

Ross

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…The findings in the present study that, following exercise training, the muscle mechanoreflex-mediated increase in MSNA is significantly diminished, and this decrease is accompanied by a significant decrease in COX-2 expression in the VL muscle, support the notion that overexpression of COX-2 in the skeletal muscle of HF patients leads to increased prostaglandin (likely PGE 2 ) sensitization of group III afferents. The expression of the EP 4 receptor, which is present on DRG and is responsible for afferent nerve sensitization by PGE 2 (52), is also decreased following exercise training. Similarly, the expression of the TP receptor, which is responsible for the afferent sensitization by TXA 2 is decreased following exercise training.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure

Antunes‐Correa

Nobre

Groehs

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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CE. Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure. Am J Physiol Heart Circ Physiol 307: H1655-H1666, 2014. First published October 10, 2014 doi:10.1152/ajpheart.00136.2014.-Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients.2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle.3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions Ͻ40% were randomized to untrained (n ϭ 17; 54 Ϯ 2 yr) or exercise-trained (n ϭ 17; 56 Ϯ 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-B/ IB-␣ ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle. heart failure; muscle sympathetic nervous system; metaboreflex; mechanoreflex; exercise training

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“…Yamauchi et al (2013) found that blocking EP4 receptors by injecting L, 161-982 into the femoral artery of a ligated rat, but not that of a freely perfused rat, attenuated the pressor response to static contraction. EP3 receptor blockade did not attenuate the response.…”

Section: Mechanisms Contributing To Exaggerated Pressor Responsementioning

confidence: 92%

The exercise pressor reflex and peripheral artery disease

Stone

Kaufman

2015

Autonomic Neuroscience

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The exercise pressor reflex contributes to increases in cardiovascular and ventilatory function during exercise. These reflexive increases are caused by both mechanical and metabolic stimulation of Group III and IV afferents with endings in contracting skeletal muscle. Patients with peripheral artery disease (PAD) have an augmented exercise pressor reflex. Recently, an animal model of PAD was established which allows further investigation of possible mechanisms involved in this augmented reflex. Earlier studies have identified ASIC3 channels, bradykinin receptors, P2X receptors, endoperoxide receptors, and thromboxane receptors as playing a role in evoking the exercise pressor reflex in healthy rats. This review focuses on recent studies using a rat model of PAD in order to determine possible mechanisms contributing to the exaggerated exercise pressor reflex seen in patients with this disease.

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Endoperoxide 4 receptors play a role in evoking the exercise pressor reflex in rats with simulated peripheral artery disease

Cited by 34 publications

References 39 publications

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Inhibition of cyclooxygenase attenuates the blood pressure response to plantar flexion exercise in peripheral arterial disease

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure

The exercise pressor reflex and peripheral artery disease

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