Increased cardiac output contributes to the development of chronic intermittent hypoxia‐induced hypertension

• Published in: Experimental physiology Vol. 99; no. 10; pp. 1312 - 1324
• Main Authors: Lucking, Eric F., O'Halloran, Ken D., Jones, James F. X.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2014
• Subjects: Animals; Aorta - physiopathology; Blood Pressure - physiology; Cardiac Output - physiology; Hematocrit; Hindlimb - blood supply; Hypertension - etiology; Hypertension - physiopathology; Hypoxia - complications; Hypoxia - physiopathology; Male; Rats; Rats, Wistar; Sympathetic Nervous System - physiopathology; Tachycardia - etiology; Tachycardia - physiopathology; Vascular Remodeling - physiology
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2014.080556

New Findings What is the central question of this study? Chronic intermittent hypoxia (CIH)‐induced hypertension is commonly believed to be a consequence of sympathetic nervous system hyperactivity, but direct recordings of chronic vasoconstriction have never been performed hitherto. We determined whether chronic vasoconstriction contributes to the development of hypertension in CIH‐exposed animals. What is the main finding and its importance? We found no evidence of chronic vasoconstriction in CIH‐exposed rats; instead, the development of hypertension was due to an increase in cardiac output. This attempt to increase O2 flow may lead to the initial development of hypertension. Increased in cardiac output has never been previously reported and could be an important parameter to measure in sleep apnoea patients. Chronic intermittent hypoxia (CIH) in animal models has been shown to result in hypertension and elevation of sympathetic nervous system activity. Sympathetically mediated vasoconstriction is believed to be the primary mechanism underpinning CIH‐induced hypertension; however, the potential contribution of the heart is largely overlooked. We sought to determine the contribution of cardiac output (CO) and lumbar sympathetic control of the hindlimb circulation to CIH‐induced hypertension. Male Wistar rats (n = 64) were exposed to 2 weeks of CIH [cycles of 90 s hypoxia (5% O2 nadir) and 210 s normoxia] or normoxia for 8 h day−1. Under urethane anaesthesia, CIH‐treated animals developed hypertension (81.4 ± 2.2 versus 91.6 ± 2.4 mmHg; P < 0.001), tachycardia (397 ± 8 versus 445 ± 7 beats min−1; P < 0.001) and an increased haematocrit (42.4 ± 0.4 versus 45.0 ± 0.4%; P < 0.001). Echocardiography revealed that CIH exposure increased the CO [19.3 ± 1.7 versus 25.8 ± 2.6 ml min−1 (100 g)−1; P = 0.027] with no change in total peripheral resistance (4.93 ± 0.49 versus 4.17 ± 0.34 mmHg ml−1 min−1; P = 0.123). Sympathetic ganglionic blockade revealed that sympathetic control over blood pressure was not different (−27.7 ± 1.6 versus −32.3 ± 2.9 mmHg; P = 0.095), and no chronic vasoconstriction was found in the hindlimb circulation of CIH‐treated animals (39.4 ± 2.5 versus 38.0 ± 2.4 μl min−1 mmHg−1; P = 0.336). Lumbar sympathetic control over the hindlimb circulation was unchanged in CIH‐treated animals (P = 0.761), although hindlimb arterial sympathetic density was increased (P = 0.012) and vascular sensitivity to phenylephrine was blunted (P = 0.049). We conclude that increased CO is sufficient to explain the development of CIH‐induced hypertension, which may be an early adaptive response to raise O2 flow. We propose that sustained elevated cardiac work may ultimately lead to heart failure.