Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation.
ABSTRACT Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. alpha,beta-Methylene ATP (alpha,beta-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as alpha,beta-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of alpha,beta-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35+/-5 (35 degrees C), 26+/-3 (37 degrees C), and 19+/-3 mmHg (39 degrees C; P<0.05 vs. 35 degrees C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when alpha,beta-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35 degrees and 37 degrees C, respectively. However, as muscle temperature reached 39 degrees C, the stretch-evoked response was augmented only 6% by alpha,beta-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35 degrees and 37 degrees C. In addition, we also examined effects of muscle temperature on alpha,beta-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37 degrees C, arterial injections of alpha,beta-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39 degrees C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.
Article: Interstitial adenosine triphosphate modulates muscle afferent nerve-mediated pressor reflex.[show abstract] [hide abstract]
ABSTRACT: Previous work has shown that muscle contraction elevates interstitial adenosine triphosphate concentration ([ATP]i), which is likely due to the release of ATP from active skeletal muscle. ATP activation of purinergic receptors P2X on thin muscle afferent fibers further enhances cardiovascular responses to contraction. Thus, the purposes of this study were: (1) to examine the mechanisms by which ATP is released from muscle in response to mechanical stimulation; and (2) to study the effects of interstitial ATP concentrations on modulating pressor response to muscle contraction. Static contraction of the triceps surae muscle was evoked by electrical stimulation (at 5 HZ and 2.5 times motor threshold) of the tibial nerve in 9 anesthetized cats. Muscle interstitial ATP samples were collected from microdialysis probes inserted into the muscles. Dialysate ATP concentrations were determined using the luciferin-luciferase assay. In a control experiment, contraction was induced after 0.5 ml of saline was injected into the arterial blood supply of the hindlimb muscles. This increased [ATP]i by 220% (P < 0.05 vs. baseline). After gadolinium (1 mM), a blocker of mechanically sensitive channels, was injected into the muscles, contraction increased [ATP]i by 112% (P < 0.05 vs. control). In contrast, glibenclamide (an inhibitor of the ATP-binding cassette protein), monensin, and brefeldin A, which interfere with vesicular formation (or trafficking) and inhibit exocytosis, did not significantly affect ATP release by muscle contraction. In addition, a regression analysis showed that [ATP]i was linearly related to the pressor response to muscle contraction. The data suggest that ATP release from skeletal muscle is mediated via involvement of mechanosensitive channels. These findings further support a physiological role for release of ATP in modulating cardiovascular responses during static muscle contraction.Muscle & Nerve 07/2008; 38(2):972-7. · 2.37 Impact Factor
Article: Exaggerated Pressor Response in Relation to Attenuated Muscle Temperature Response during Contraction in Ischemic Heart Failure.[show abstract] [hide abstract]
ABSTRACT: It is known that muscle temperature (T(m)) increases with exercise. The purpose of this study was to examine if contraction-induced increase in T(m) was altered in rats with heart failure (HF) induced by chronic myocardial infraction (MI) as compared with healthy control animals. A temperature probe was inserted in the triceps surae muscle to continuously measure T(m) throughout experiments. Static muscle contraction was induced by electrical stimulation of the sciatic nerve for 1 min. As baseline T(m) was 34°C, contraction increased temperature by 1.6 ± 0.18°C in nine health control rats and by 1.0 ± 0.15°C in 10 MI rats (P < 0.05 vs. control). Note that there were no differences in developed muscle tension and muscle weight between the two groups. In addition, muscle contraction increased mean arterial pressure by 23 ± 3 mmHg in control rats and by 31 ± 3 mmHg in MI rats (P < 0.05 vs. control). A regression analysis further shows that there is an inverse liner relationship between the pressor response and static contraction-induced increase in T(m). Our data suggest that T(m) increase evoked by contraction is impaired in MI rats. The abnormal alteration in T(m) likely modifies the reflex cardiovascular responses in MI via mechanisms of temperature-sensitive receptors on muscle afferent nerves.Frontiers in physiology. 01/2012; 3:443.