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UBC Theses and Dissertations

The role of the angiotensin-II type I receptor in the control of breathing and central sleep apnea in normobaric hypoxia. Brown, Courtney


Nearly all healthy humans experience central sleep apnea (CSA) at high altitude (>4000 m). Sensitization of the carotid body (CB), the primary peripheral chemoreceptor (PCR), is thought to facilitate the enhanced ventilatory response to carbon dioxide (CO₂) and the development of CSA following hypoxic exposure. A local renin-angiotensin system within the CB and the angiotensin II type-I receptor (AT₁R) may play an important role in this pathway. We aimed to determine if losartan, an AT₁R antagonist, attenuates chemosensitization of the PCR and consequently the severity of hypoxia induced CSA. We hypothesized that losartan would attenuate CSA severity and PCR chemosensitivity. In a double blind, placebo-controlled, randomized cross-over study, male participants (n = 14) took either losartan or a placebo pill three times over 24 hours on experimental days. Sleep in a normobaric hypoxic chamber (FIO₂ = 0.135) was monitored using a type-I cardiopulmonary sleep system. Chemosensitivity was assessed using hypercapnic ventilatory response (HCVR) tests and a hypoxic apnea response (HAR) test and was completed prior to and following eight hours of sleep in hypoxia. HCVR tests were conducted in a hyperoxic (PETO₂ = 350 mmHg) and hypoxic (PETO₂ = 50 mmHg) background. The HAR consisted of 2 breaths of nitrogen (N₂) followed by a 20 second apnea and 40 seconds of recovery repeated 6 times. Compared to placebo, losartan did not reduce CSA severity (73 ± 15 and 75 ± 14, respectively; P = 0.8). Ventilatory reactivity was similar between losartan and placebo during the hyperoxic HCVR (3.6 ± 1.1 and 4.0 ± 0.6 l/min/mmHg, respectively; P = 0.4) and the hypoxic HCVR (5.3 ± 1.4 and 5.7 ± 0.7 l/min/mmHg, respectively; P = 0.9). Losartan did not affect the cardiorespiratory responses to hypoxic apneas. In summary, losartan did not reduce CSA severity, or the chemoreflex responsiveness before or after eight hours of acute nocturnal hypoxia. Therefore, the AT1R may not be involved in the chemosensitization of the PCR or the development of CSA in response to acute nocturnal hypoxia, in healthy young males.

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