Chronic intermittent hypoxia and ovariectomy exert independent and region-specific effects on ΔFosB expression and increase blood pressure in female rats.

Abstract

Chronic intermittent hypoxia (CIH), a preclinical model of hypoxemia associated with sleep apnea, causes hypertension associated with increased sympathetic activity linked to arterial chemoreflex and renin-angiotensin system activation. In some models of CIH, ovarian hormones have a protective effect against the change in blood pressure. We tested the effects of CIH and ovariectomy (OVX) on blood pressure and ΔFosB expression in female Sprague-Dawley rats. We hypothesized that CIH and OVX would increase ΔFosB in central autonomic regions associated with increases in blood pressure. Intact (INT) and OVX adult female Sprague-Dawley rats were exposed to 7 days of CIH only during the light (sleep) phase or continuous normoxia (CON). Mean arterial pressure (MAP) was continuously monitored by radiotelemetry. Rats were anesthetized with Inactin and euthanized, and brains were collected and processed for immunohistochemistry. CIH increased MAP relative to CON during the light phase, regardless of gonadal status. During the dark (active) phase, an increase in MAP was observed in OVX but not in INT rats, irrespective of CIH. CIH significantly increased ΔFosB immunoreactive cells in the caudal nucleus of the solitary tract, A5 region, and rostral ventrolateral medulla regardless of OVX. Independent of CIH, OVX significantly increased ΔFosB immunoreactive cells in the organum vasculosum of the lamina terminalis, median preoptic nucleus, rostral nucleus tractus solitarius, and the dorsal, medial, and lateral parvocellular subdivisions of the paraventricular nucleus. Our data indicate that CIH and OVX increase blood pressure independently and exert region-specific effects on ΔFosB immunoreactivity in central autonomic regions.NEW & NOTEWORTHY We investigated the effects of ovarian hormone depletion and chronic intermittent hypoxia (CIH) on blood pressure and ΔFosB staining in central autonomic regions. Our findings indicate that ovariectomy (OVX) and CIH have independent effects on blood pressure and produce region-specific changes in ΔFosB staining in the central autonomic regions associated with hypertension. This suggests that the effects of CIH and OVX on ΔFosB staining and hypertension are not additive.