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1 Department of Comparative Biosciences, University of Wisconsin, Madison, WI, USA
2 Population Health Sciences, University of Wisconsin, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: zabkaa{at}svm.vetmed.wisc.edu.
Age and the estrus cycle affect time-dependent respiratory responses to episodic hypoxia in female rats. Long-term facilitation (LTF), a form of serotonin-dependent respiratory plasticity, is enhanced in middle-aged versus young female rats (and in diestrus versus estrus) (72). We tested the hypothesis that phrenic and hypoglossal (XII) LTF are diminished in geriatric rats after they stop cycling and fluctuating sex hormone levels no longer establish conditions necessary for LTF. Chronic intermittent hypoxia (CIH) enhances LTF (41); thus, we further predicted that CIH would restore phrenic and XII LTF in geriatric female rats. LTF was measured in young (3-4 mo) and geriatric (20-22 mo) female Sasco Sprague Dawley rats and in a group of geriatric rats exposed to one week of nocturnal CIH (11%/21% O2 at 5 min intervals, 12 hrs/night). In anesthetized, paralyzed, vagotomized and ventilated rats, time-dependent hypoxic phrenic and XII responses were assessed. The short-term hypoxic response (STHR) was measured during the first of 3, 5-min episodes of isocapnic hypoxia (PaO2 35-45 mmHg). LTF was assessed 15, 30 and 60 min post-episodic hypoxia. Phrenic and XII STHR were not different among groups, regardless of CIH treatment (p>0.05). LTF in geriatric female rats was smaller than previously reported for middle-aged rats, but comparable to young female rats. CIH augmented phrenic and XII LTF to levels similar to middle-aged female rats without CIH (p<0.05). The magnitude of phrenic and XII LTF in all groups was inversely related to the ratio of progesterone/estradiol serum levels (p<0.05). Thus, CIH and sex hormones influence the magnitude of LTF in geriatric female rats.
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