Acute hypoxia alters reflex micturition behavior in urethane‐anesthetized carotid sinus intact and denervated adult female Sprague‐Dawley rat

Abstract

Acute hypoxia is well known to increase respiratory drive by stimulating peripheral chemoreceptors located in the carotid bodies. Ongoing work in our laboratory has been examining the effects acute hypoxia on lower urinary tract (LUT) function in urethane‐anesthetized adult female rats. While these experiments have revealed that exposure to acute hypoxia is capable of modifying LUT function, the contribution of peripheral chemoreceptor‐mediated effects is unknown. Moreover, hypoxia‐induced modulation of LUT behavior is present both during hypoxia and transiently after the hypoxic stimulus is removed, such that hypoxia increases void frequency while the return to normoxia increases the threshold bladder pressure for voiding and prolongs the inter‐contraction interval (ICI). The present study was designed to evaluate whether the changes in LUT function noted are mediated by mechanisms that are dependent on carotid body hypoxia chemoreception. To this end, we conducted a series of experiments using continuous flow bladder cystometry with simultaneous recording of external urethral sphincter (EUS) EMG activity in urethane‐anesthetized spontaneously breathing adult female Sprague‐Dawley rats (n=10). Micturition events were elicited by saline infusion into the bladder via suprapubic catheter with the saline flow rate adjusted to induce a voiding frequency of approximately one void every 4–5 minutes. We also simultaneously recorded tongue, external oblique, and diaphragm muscle EMG activity via bipolar stainless steel EMG electrodes. Each rat was allowed to settle into a stable baseline voiding rhythm which was then recorded for approximately 1‐hr under normoxic conditions, after which an hypoxic challenge (12% O2, 15 min) was performed. In one group of rats, the carotid sinus nerves (CSN) were transected bilaterally prior to beginning the cytometry experiment while in a second group of rats the CSN were left intact. Success of the CSN denervation was confirmed by the absence of an increase in diaphragm EMG burst amplitude and frequency during the hypoxic challenge. Consistent with our prior observations, CSN intact rats responded to hypoxia with an increased voiding frequency, particularly at the onset of hypoxia; however, peak bladder pressure during contraction was variable with no consistent modulation by hypoxia. Upon return to normoxia, the initial voiding event was delayed, and subsequent events displayed increased ICI with elevated bladder pressure threshold. In contrast to CSN intact rats, CSN denervated rats exhibited a marked decrease in peak bladder contraction pressure during hypoxic exposure as well as a smaller increase in bladder pressure threshold after return to normoxia. No notable differences in hypoxia‐induced changes in ICI between CSN intact or transected rats was observed. These results suggest that hypoxia‐mediated carotid body afferent input is not required for producing a modulation of reflex micturition in response to hypoxia, but certain aspects of the hypoxic response may be impacted by carotid body dependent mechanisms.Support or Funding InformationNIH NS096514This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.