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

Abstract

Schmitt, Petra M., and Marc P. Kaufman. Estrogen's attenuating effect on the exercise pressor reflex is more opioid dependent in gonadally intact than in ovariectomized female cats. J Appl Physiol 98: 633-639, 2005. First published September 24, 2004 doi:10.1152/ japplphysiol.00788.2004.-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 l of 17␤-estradiol (0.01 g/ml) with and without the addition of 1,000 g naloxone, a -and ␦-opioid antagonist, to a spinal well covering the L 6-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 L 7 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 Ϯ 4 mmHg (n ϭ 10), whereas the pressor response 60 min afterward averaged only 18 Ϯ 4 mmHg (P Ͻ 0.05). In contrast, the pressor response to contraction before estrogen and naloxone application averaged 33 Ϯ 5 mmHg (n ϭ 11), whereas afterward it averaged 27 Ϯ 6 mmHg (P Ͻ 0.05). In ovariectomized cats, naloxone was less effective in reversing the attenuating effect of estrogen on the exercise pressor reflex. sex hormones; static contraction; blood pressure; neural control of circulation; autonomic nervous system THE EXERCISE PRESSOR REFLEX consists of increases in mean arterial pressure, heart rate and ventilation that are evoked by static contraction of the hindlimb muscles in anesthetized or decerebrated animals (19). Recently, spinally applied estrogen was found to attenuate the arterial pressure component of the exercise pressor reflex in decerebrated cats. This attenuation was shown to be gender specific because the threshold concentration of estrogen needed to attenuate the pressor response to contraction was 1,000 times more dilute in female cats than it was in male cats (24,25).The mechanism by which spinally applied estrogen attenuated the reflex pressor response to static contraction is unknown. Nevertheless, -opioid receptors and ␦-opioid receptors have been implicated in the spinal regulation of the exercise pressor ...

Passive limb movement: evidence of mechanoreflex sex specificity

“…Furthermore, in agreement with the results of Jarvis et al (28), the present findings may also not depend on estrogen per se, as these experiments were performed in the early follicular phase of the menstrual cycle, where estrogen is at low levels, similar to that of men (15,21,56). Schmitt et al (53) indicated that, while the exercise pressor reflex can be suppressed by estrogen, there appears to be cross-talk between the estrogen and opioid systems, suggesting an indirect effect of estrogen. Therefore, in combination, the results from present and previous studies suggest that through either direct or indirect mechanisms, the presence of estrogen and/or other factors associated with being female appear to blunt both group III (mechanosensitive) and group IV (metabosensitive) afferent feedback and subsequent cardioacceleration.…”

“…The results from Jarvis et al (28) suggest that the sex differences during hand- In support of this reduced afferent signaling in women, the present findings suggest that women display attenuated group III afferent nerve or mechanoreceptor sensitivity, as evidenced by a lower CO response to passive limb movement. Although the mechanism responsible for this attenuation was not elucidated in the present study, previous work (51)(52)(53)(54) performed using an animal model has determined that estrogen, either endogenously or via spinal application, can attenuate the exercise pressor reflex in both male and female rats. This implies a significant role of estrogen in modulating afferent nerve signaling and the subsequent exercise pressor reflex (51)(52)(53)(54).…”

“…Although the mechanism responsible for this attenuation was not elucidated in the present study, previous work (51)(52)(53)(54) performed using an animal model has determined that estrogen, either endogenously or via spinal application, can attenuate the exercise pressor reflex in both male and female rats. This implies a significant role of estrogen in modulating afferent nerve signaling and the subsequent exercise pressor reflex (51)(52)(53)(54). However, recent data from humans has suggested that a sexspecific effect of the exercise pressor reflex persists across the menstrual cycle, where endogenous hormones (estrogen and progesterone) oscillate from low to high concentrations, casting doubt on the estrogen dependence of this phenomenon (28).…”

Estradiol interacts with an opioidergic network to achieve rapid modulation of a vocal pattern generator

“…Antagonists included the broad-spectrum opioid receptor antagonist naloxone (1, 10, 25 mM; n  = 6, 4, 4 animals each, respectively), the mu-specific opioid antagonist beta-funaltrexamine (1, 10 mM; n  = 4 each), and the kappa-specific opioid antagonist nor-binaltorphimine (0.66, 6.6 mM; n  = 3 each). Drug doses were based on previous studies of opioid–steroid interactions (Evans et al 2000; Acosta-Martinez and Etgen 2002; Ceccarelli et al 2004; Schmitt and Kaufman 2005). The standard dose sequence (1, 10 mM) was lowered slightly for nor-binaltorphimine due to limited reagent availability; it is an effective kappa-opioid antagonist in both mammalian and non-mammalian vertebrates (Bradford et al 2005).…”

The Muscle Stretch Reflex throughout the Menstrual Cycle

“…However, another study failed to demonstrate any significant differences in the maximal elongation or stiffness of the patellar tendon across the menstrual cycle (22). It also appears that these hormones might have neurosteroidal effects that can potentially alter neural transmission through the peripheral nervous system, spinal cord and brain (32, 37). In light of the potential for female sex hormones to modulate connective tissue mechanics and neural circuitry, a handful of studies have investigated changes in motor control throughout the menstrual cycle.…”