Sustained Hypoxia and the Renin Angiotensin System

Date
2014
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Abstract
Rationale: Chronic tissue hypoxia is considered to be the unifying pathway in chronic kidney disease (CKD) progression, yet the effect of systemic hypoxia as manifested in obstructive sleep apnea (OSA) is not well understood. Limited studies suggest OSA is associated with upregulation of the renin angiotensins system (RAS) a well described pathogenic factor renal dysfuction. We sought to determine the effect of nocturnal hypoxia on the hemodynamic and circulating response to angiotensin II (AngII) infusion. Methods: Thirty-one OSA patients (14 newly diagnosed; 17 from a historic cohort) and twelve obese controls were studied. Effective renal plasma flow (ERPF), determined by para-aminohippurate clearance technique, blood pressure (BP) and circulating components of the RAS (plasma renin activity (PRA) and aldosterone) were measured at baseline and in response to angiotensin-II (AngII) infusion. Patients were stratified according to hypoxia severity, into those with IH (mean nocturnal SaO2≥90%) and sustained hypoxia (SH, mean nocturnal SaO2<90%). Results: Patients with SH (P=0.015) and IH (P=0.01) had higher baseline filtration fractions (FF) than obese controls but circulating RAS components and BP were similar. The fall in ERPF in response to AngII, was less in patients with SH than IH and obese controls after both 3ng/kg/min (P=0.004) and 6ng/kg/min (P=0.001) reflecting greater renal RAS activity. There were no differences in the BP or PRA responses, but SH patients had a more robust aldosterone response to 6ng/kg/min AngII (p=0.023) than patients with IH. Conclusion: In patients with OSA, SH is associated with greater renal RAS activity than IH. OSA patients with this hypoxia profile may be more likely to experience the vascular consequences of elevated RAS activity such as hypertension and CKD.
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Medicine and Surgery
Citation
Zalucky, A. (2014). Sustained Hypoxia and the Renin Angiotensin System (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27945