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

Abstract

New Findings r 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. r 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 O 2 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% O 2 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 1313 Development of chronic intermittent hypoxia-induced hypertension early adaptive response to raise O 2 flow. We propose that sustained elevated cardiac work may ultimately lead to heart failure.

Development of hypertension in chronic intermittent hypoxia: is it driven by cardiac output rather than by peripheral resistance?

“…Lucking et al . () support their conclusion with the finding that baseline hindlimb vascular conductance was not altered by CIH. Furthermore, hexamethonium caused similar vasodilatation in the hindlimbs of control rats and those exposed to 2 weeks of CIH, suggesting no difference in sympathetic vasoconstrictor tone.…”

“…Additional findings made by Lucking et al . () may explain this paradox. Chronic intermittent hypoxia enhanced the elastin content and increased the compliance of the aorta, which should help to buffer rises in ABP caused by peripheral vasoconstriction.…”

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

“…Additionally, there is growing literature about the prevalence of chronic obstructive pulmonary disease (COPD) in patients with CKD (11,12). Notwithstanding etiology, hypoxemia and hypoxia are associated with a host of acute and chronic sequelae affecting multiple organ systems (13)(14)(15), including the cardiovascular system (16,17), wound healing (18), proinflammatory pathways (19), and the central nervous system (20). Some of these pathologies are highly prevalent in patients on hemodialysis (for example, inflammation and changes in vascular smooth muscles and endothelium, processes that accelerate arteriosclerosis) (21,22).…”

Augmented cardiovascular responses to episodes of repetitive compared with isolated respiratory events in preschool children with sleep-disordered breathing

“…Rodent models of long-term intermittent hypoxia have demonstrated hypertension and increased sympathetic activity (22), increased right ventricular systolic pressure, right ventricular mass, neovascularization of distal pulmonary vessels (23), systemic and pulmonary vascular pressure (24,25), cardiac hypertrophy, and cardiac and perivascular fibrosis (26). Previous studies in children have however not found a strong link between arterial desaturation and elevated HR and BP (27).…”