(Hypertension. 1999;34:309-314.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Renin Activity and Blood Pressure in Response to Chronic Episodic Hypoxia
From the Department of Medicine, Division of Respiratory, Environmental and Critical Care Medicine, Louisville Veterans Affairs Medical Center and the University of Louisville School of Medicine, Louisville, Ky.
Correspondence to Eugene C. Fletcher, MD, Professor of Medicine, Division of Respiratory, Critical Care and Environmental Medicine, University of Louisville School of Medicine, Ambulatory Care Building, Room A3L01, 530 S Jackson St, Louisville, KY 40292.
Abstract—Previous studies in several strains of rats have demonstrated that 35 days of recurrent episodic hypoxia (EH) (7 hours per day), with a fractional concentration of inspired oxygen that produces desaturation equivalent to the recurrent hypoxemia of sleep apnea, results in an 8 to 13 mm Hg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. Both renal artery denervation and adrenal demedullation block the BP response to chronic EH. The present study was undertaken to define further the role of the kidneys and the renin-angiotensin system in this BP increase. Separate groups of male Sprague-Dawley rats had either (1) bilateral renal artery denervation with EH, (2) sham surgery with EH, (3) sham surgery with sham EH (compressed air), (4) EH with losartan, (5) unhandled with losartan, or (6) unhandled. The experimental period lasted 35 days. Both renal-artery denervated and losartan-treated animals showed no BP change or a lowering of BP in response to EH, whereas the sham-operated EH animals showed a progressive, sustained increase in resting room air BP. BP remained at basal levels or fell in unhandled and unhandled losartan-treated animals. Plasma renin activity was elevated 4-fold versus basal levels in EH animals with renal nerves intact but remained at baseline levels in denervated animals. At the end of the experiment, renal tissue catecholamines confirmed renal denervation in those animals. In conclusion, EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotensin II type 1 receptors.
Key Words: hypoxia • blood pressure • denervation, renal • sympathetic nervous system • sleep apnea syndromes • hypertension, systemic • renin-angiotensin system
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