High concentrations of 17β-estradiol attenuate the exercise pressor reflex in male cats

2003 ◽  
Vol 94 (4) ◽  
pp. 1431-1436 ◽  
Author(s):  
Petra M. Schmitt ◽  
Marc P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Muscle Afferents ◽  
Central Command ◽  
Physiological Level ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
High Concentrations ◽  
Decerebrate Cats

Previously, intravenous injection of 17β-estradiol in decerebrate male cats was found to attenuate central command but not the exercise pressor reflex. This latter finding was surprising because the dorsal horn, the spinal site receiving synaptic input from thin-fiber muscle afferents, is known to contain estrogen receptors. We were prompted, therefore, to reexamine this issue. Instead of injecting 17β-estradiol intravenously, we applied it topically to the L7 and S1 spinal cord of male decerebrate cats. We found that topical application (150–200 μl) of 17β-estradiol in concentrations of 0.01, 0.1, and 1 μg/ml had no effect on the exercise pressor reflex, whereas a concentration of 10 μg/ml attenuated the reflex. We conclude that, in male cats, estrogen can only attenuate the exercise pressor reflex in concentrations that exceed the physiological level.

Estrogen attenuates the exercise pressor reflex in female cats

2003 ◽  
Vol 95 (4) ◽  
pp. 1418-1424 ◽  
Author(s):  
Petra M. Schmitt ◽  
M. P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Pressor Response ◽  
Muscle Afferents ◽  
Threshold Concentration ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Reflex Arc ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
The Difference

In humans, the pressor and muscle sympathetic nerve responses to static exercise are less in women than in men. The difference has been attributed to the effect of estrogen on the exercise pressor reflex. Estrogen receptors are abundant in areas of the dorsal horn receiving input from group III and IV muscle afferents, which comprise the sensory limb of the exercise pressor reflex arc. These findings prompted us to investigate the effect of estrogen on the spinal pathway of the exercise pressor reflex arc. Previously, we found that the threshold concentration of 17β-estradiol needed to attenuate the exercise pressor reflex in male decerebrate cats was 10 μg/ml (Schmitt PM and Kaufman MP. J Appl Physiol 94: 1431-1436, 2003). The threshold concentration for female cats, however, is not known. Consequently, we applied 17β-estradiol to a well covering the L6-S1 spinal cord in decerebrate female cats. The exercise pressor reflex was evoked by electrical stimulation of the L7 or S1 ventral root, a maneuver that caused the hindlimb muscles to contract statically. We found that the pressor response to contraction averaged 38 ± 7 mmHg before the application of 17β-estradiol (0.01 μg/ml) to the spinal cord, whereas it averaged only 23 ± 4 mmHg 30 min after application ( P < 0.05). Recovery of the pressor response to contraction was not obtained for 2 h after application of 17β-estradiol. Application of 17β-estradiol in a dose of 0.001 μg/ml had no effect on the exercise pressor reflex ( n = 5). We conclude that the concentration of 17β-estradiol required to attenuate the exercise pressor reflex is 1,000 times more dilute in female cats than that needed to attenuate this reflex in male cats.

scholarly journals Both central command and exercise pressor reflex activate cardiac sympathetic nerve activity in decerebrate cats

2009 ◽  
Vol 296 (4) ◽  
pp. H1157-H1163 ◽  
Author(s):  
Hirotsugu Tsuchimochi ◽  
Shawn G. Hayes ◽  
Jennifer L. McCord ◽  
Marc P. Kaufman
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ventral Root ◽  
Central Command ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Exercise Pressor Reflex ◽  
Cardiac Sympathetic Nerve Activity ◽  
Pressor Reflex ◽  
Decerebrate Cats

Both static and dynamic exercise are known to increase cardiac pump function as well as arterial blood pressure. Feedforward control by central command and feedback control by the exercise pressor reflex are thought to be the neural mechanisms causing these effects during exercise. It remains unknown as to how each mechanism activates cardiac sympathetic nerve activity (CSNA) during exercise, especially at its onset. Thus we examined the response of CSNA to stimulation of the mesencephalic locomotor region (MLR, i.e., central command) and to static muscle contraction of the triceps surae muscles or stretch of the calcaneal tendon in decerebrate cats. We found that MLR stimulation immediately increased CSNA, which was followed by a gradual increase in heart rate, mean arterial pressure, and ventral root activity in a stimulus intensity-dependent manner. The latency of the increase in CSNA from the onset of MLR stimulation ranged from 67 to 387 ms. Both static contraction and tendon stretch also rapidly increased CSNA. Their latency from the development of tension in response to ventral root stimulation ranged from 78 to 670 ms. These findings suggest that both central command and the muscle mechanoreflex play a role in controlling cardiac sympathetic outflow at the onset of exercise.

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats

2002 ◽  
Vol 92 (4) ◽  
pp. 1635-1641 ◽  
Author(s):  
Shawn G. Hayes ◽  
Nicolas B. Moya Del Pino ◽  
Marc P. Kaufman
Keyword(s):  
Triceps Surae ◽  
Central Command ◽  
Neuronal Function ◽  
Ventilatory Responses ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Static Contraction ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17β-estradiol; 0.001, 0.01, 0.1, and 1.0 μg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17β-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17β-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.

Spinal estrogen attenuates the exercise pressor reflex but has little effect on the expression of genes regulating neurotransmitters in the dorsal root ganglia

2006 ◽  
Vol 100 (3) ◽  
pp. 958-964 ◽  
Author(s):  
Petra M. Schmitt ◽  
Kishorchandra Gohil ◽  
Marc P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Mrna Expression ◽  
Dorsal Root ◽  
Pressor Response ◽  
Muscle Afferents ◽  
Female Rats ◽  
Opioid Antagonist ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Pressor Reflex

Previously, our laboratory showed that estrogen, topically applied to the spinal cord, attenuated the exercise pressor reflex in female cats (Schmitt PM and Kaufman MP. J Appl Physiol 95: 1418–1424, 2003; 98: 633–639, 2005). The attenuation was gender specific and was in part opioid dependent. Our finding that the μ- and δ-opioid antagonist naloxone was only able to partially restore estrogen’s attenuating effect on the pressor response to static contraction suggested that estrogen affected an additional pathway, involving the dorsal root ganglion (DRG). Estrogen has been described to stimulate transcription within 10 min of its application to the DRG, raising the possibility that rapid genomic effects on neurotransmitter production may have contributed to estrogen’s effect on the exercise pressor reflex. This prompted us to test the hypothesis that estrogen modulated the pressor response to static contraction by influencing gene expression of the neurotransmitters released by the thin-fiber muscle afferents that evoke the exercise pressor reflex. We confirmed in decerebrated female rats that topical application of estrogen (0.01 μg/ml) to the lumbosacral spinal cord attenuated the pressor response to static muscle contraction (from 10 ± 3 to 1 ± 1 mmHg; P < 0.05). DRG were then harvested postmortem, and changes in mRNA expression were analyzed. GeneChip analysis revealed that neither estrogen nor contraction alone changed the mRNA expression of substance P, the neurokinin-1 receptor, CGRP, NGF, the P2X3 receptor, GABAA and GABAB, the 5-HT3A and 5-HT3B receptor, N-methyl-d-aspartate and non- N-methyl-d-aspartate receptors, opioid receptors, and opioid-like receptor. Surprisingly, however, contraction stimulated the expression of neuropeptide Y in the DRG in the presence and absence of estrogen. We conclude that estrogen does not attenuate the exercise pressor reflex through a genomic effect in the DRG.

scholarly journals Femoral artery ligation increases the responses of thin-fiber muscle afferents to contraction

2015 ◽  
Vol 113 (10) ◽  
pp. 3961-3966 ◽  
Author(s):  
Audrey J. Stone ◽  
Steven W. Copp ◽  
Jennifer L. McCord ◽  
Marc P. Kaufman
Keyword(s):  
Femoral Artery ◽  
Muscle Afferents ◽  
Group Iv ◽  
Artery Ligation ◽  
Thin Fiber ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Hindlimb Muscles ◽  
Static Contraction ◽  
Pressor Reflex

Previous evidence has shown that ligating the femoral artery for 72 h resulted in an exaggerated exercise pressor reflex. To provide electrophysiological evidence for this finding, we examined in decerebrated rats whose femoral arteries were either freely perfused or ligated for 72 h the responses of thin-fiber (i.e., groups III and IV) afferents to static contraction of the hindlimb muscles. We found that contraction increased the combined activity of group III and IV afferents in both freely perfused ( n = 29; baseline: 0.3 ± 0.1 imp/s, contraction: 0.8 ± 0.2 imp/s; P < 0.05) and ligated rats ( n = 28; baseline: 0.4 ± 0.1 imp/s, contraction: 1.4 ± 0.1 imp/s; P < 0.05). Most importantly, the contraction-induced increase in afferent activity was greater in ligated rats than it was in freely perfused rats ( P = 0.005). In addition, the responses of group III afferents to contraction in ligated rats ( n = 15; baseline 0.3 ± 0.1 imp/s, contraction 1.5 ± 0.2 imp/s) were greater ( P = 0.024) than the responses to contraction in freely perfused rats ( n = 18; baseline 0.3 ± 0.1 imp/s, contraction 0.9 ± 0.2 imp/s). Likewise, the responses of group IV afferents to contraction in ligated rats ( n = 13; baseline 0.5 ± 0.1 imp/s, contraction 1.3 ± 0.2 imp/s) were greater ( P = 0.048) than the responses of group IV afferents in freely perfused rats ( n = 11; baseline 0.3 ± 0.1 imp/s, contraction 0.6 ± 0.2 imp/s). We conclude that both group III and IV afferents contribute to the exaggeration of the exercise pressor reflex induced by femoral artery ligation.

scholarly journals P2X2/3 and P2X3 receptors contribute to the metaboreceptor component of the exercise pressor reflex

2010 ◽  
Vol 109 (5) ◽  
pp. 1416-1423 ◽  
Author(s):  
Jennifer L. McCord ◽  
Hirotsugu Tsuchimochi ◽  
Marc P. Kaufman
Keyword(s):  
Pressor Response ◽  
P2x Receptors ◽  
Triceps Surae ◽  
P2x3 Receptor ◽  
P2x3 Receptors ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Metabolic Component ◽  
Pressor Reflex ◽  
Decerebrate Cats

The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of α,β-methylene ATP (α,β-MeATP; 50 μg/kg), freely perfused static contraction, contraction of the triceps surae muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to α,β-MeATP injection (before Δ 20 ± 3 mmHg; drug Δ 11 ± 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (before Δ 33 ± 5 mmHg; drug Δ 15 ± 5 mmHg; P < 0.05), contraction with the circulation occluded (before Δ 52 ± 7 mmHg; drug Δ 20 ± 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (before Δ 15 ± 1 mmHg; drug Δ 5 ± 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.

scholarly journals Chondroitin sulfate attenuates acid-induced augmentation of the mechanical response in rat thin-fiber muscle afferents in vitro

2019 ◽  
Vol 126 (4) ◽  
pp. 1160-1170 ◽  
Author(s):  
Norio Hotta ◽  
Asako Kubo ◽  
Kazue Mizumura
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Mechanical Response ◽  
Muscle Afferents ◽  
Chondroitinase Abc ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Significant Difference ◽  
Muscle Mechanoreflex ◽  
Pressor Reflex

Exercise-induced tissue acidosis augments the exercise pressor reflex (EPR). One reason for this may be acid-induced mechanical sensitization in thin-fiber muscle afferents, which is presumably related to EPR. Acid-induced sensitization to mechanical stimulation has been reported to be attenuated in cultured primary-sensory neurons by exogenous chondroitin sulfate (CS) and chondroitinase ABC, suggesting that the extracellular matrix CS proteoglycan is involved in this sensitization. The purpose of this study was to clarify whether acid-induced sensitization of the mechanical response in the thin-fiber muscle afferents is also suppressed by exogenous CS and chondroitinase ABC using a single-fiber recording technique. A total of 88 thin fibers (conduction velocity <15.0 m/s) dissected from 86 male Sprague-Dawley rats were identified. A buffer solution at pH 6.2 lowered their mechanical threshold and increased their response magnitude. Five minutes after CS (0.3 and 0.03%) injection near the receptive field, these acid-induced changes were significantly reduced. No significant difference in attenuation was detected between the two CS concentrations. Chondroitinase ABC also significantly attenuated this sensitization. The control solution (0% CS) did not significantly alter the mechanical sensitization. Furthermore, no significant differences were detected in this sensitization and CS-based suppression between fibers with and without acid-sensitive channels [transient receptor potential vanilloid 1 (TRPV1), acid-sensing ion channel (ASIC)]. In addition, this mechanical sensitization was not changed by TRPV1 and ASIC antagonists, suggesting that these ion channels are not involved in the acid-induced mechanical sensitization of muscle thin-fiber afferents. In conclusion, CS administration has a potential to attenuate the acidosis-induced exaggeration of muscle mechanoreflex. NEW & NOTEWORTHY We found that exogenous chondroitin sulfate attenuated acid-induced mechanical sensitization in thin-fiber muscle afferents that play a crucial role in the exercise pressor reflex. This finding suggests that extracellular matrix chondroitin sulfate proteoglycans may be involved in the mechanism of acid-induced mechanical sensitization and that daily intake of chondroitin sulfate may potentially attenuate this amplification of muscle mechanoreflex and therefore reduce muscle pain related to acidic muscle conditions.

scholarly journals Role played by acid-sensitive ion channels in evoking the exercise pressor reflex

2008 ◽  
Vol 295 (4) ◽  
pp. H1720-H1725 ◽  
Author(s):  
Shawn G. Hayes ◽  
Jennifer L. McCord ◽  
Jon Rainier ◽  
Zhuqing Liu ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Ion Channels ◽  
Sodium Channels ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Pressor Reflex

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half ( P < 0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

Estrogen’s attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats

2005 ◽  
Vol 98 (2) ◽  
pp. 633-639 ◽  
Author(s):  
Petra M. Schmitt ◽  
Marc P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Pressor Response ◽  
Opioid Antagonist ◽  
Intact Female ◽  
Exercise Pressor Reflex ◽  
Hindlimb Muscles ◽  
Static Contraction ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
Stimulation Of

Using gonadally intact female cats, we showed previously that estrogen, applied topically to the spinal cord, attenuated the exercise pressor reflex. Although the mechanism by which estrogen exerted its attenuating effect is unknown, this steroid hormone has been shown to influence spinal opioid pathways, which in turn have been implicated in the regulation of the exercise pressor reflex. These findings prompted us to test the hypothesis that opioids mediate the attenuating effect of estrogen on the exercise pressor reflex in both gonadally intact female and ovariectomized cats. We therefore applied 200 μl of 17β-estradiol (0.01 μg/ml) with and without the addition of 1,000 μg naloxone, a μ- and δ-opioid antagonist, to a spinal well covering the L6–S1 spinal cord in decerebrated female cats that were either gonadally intact or ovariectomized. The exercise pressor reflex was evoked by electrical stimulation of the L7 or S1 ventral root, a maneuver that caused the hindlimb muscles to contract statically. We found that, in gonadally intact cats, the attenuating effect of estrogen was more pronounced than that in ovariectomized cats. We also found that, in gonadally intact female cats, naloxone partly reversed the attenuation of the pressor response to static contraction caused by spinal estrogen application. For example, in intact cats, the pressor response to contraction before estrogen application averaged 39 ± 4 mmHg ( n = 10), whereas the pressor response 60 min afterward averaged only 18 ± 4 mmHg ( P < 0.05). In contrast, the pressor response to contraction before estrogen and naloxone application averaged 33 ± 5 mmHg ( n = 11), whereas afterward it averaged 27 ± 6 mmHg ( P < 0.05). In ovariectomized cats, naloxone was less effective in reversing the attenuating effect of estrogen on the exercise pressor reflex.

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