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. 2023:1427:43-51.
doi: 10.1007/978-3-031-32371-3_5.

Three Days of Chronic Intermittent Hypoxia Induce β1-Adrenoceptor Dependent Increases in Left Ventricular Contractility

Anthony L Marullo  1 , Eric F Lucking  1 , Daniel Pender  1 , Pardeep Dhaliwal  1 , Ken D O'Halloran  2
Affiliations

Three Days of Chronic Intermittent Hypoxia Induce β1-Adrenoceptor Dependent Increases in Left Ventricular Contractility

Anthony L Marullo et al. Adv Exp Med Biol. 2023.

Abstract

Sleep apnea is characterized by bouts of chronic intermittent hypoxia (CIH) that elicit sympathetic hyperactivity resulting in residual hypertension. We previously demonstrated that exposure to CIH increases cardiac output and sought to determine if enhanced cardiac contractility manifests prior to hypertension.Male Wistar rats were exposed to cyclical bouts of hypoxia (FiO2 = 0.05 nadir; 90 s) and normoxia (FiO2 = 0.21; 210 s) 8 h/day for 3 days (CIH; n = 6). Control animals (n = 7) were exposed to room air. Data are presented as mean ± SD and were analyzed using unpaired Student t-tests.Three-day exposure to CIH did not elicit changes in heart rate and blood pressure (p > 0.05). However, baseline left ventricular contractility (dP/dtMAX) was significantly increased in CIH-exposed animals compared with control (15300 ± 2002 vs. 12320 ± 2725 mmHg/s; p = 0.025), despite no difference in catecholamine concentrations. Acute β1-adrenoceptor inhibition reduced contractility in CIH-exposed animals (-7604 ± 1298 vs. -4747 ± 2080 mmHg/s; p = 0.014), to levels equivalent to control, while preserving cardiovascular parameters. Sympathetic ganglion blockade (hexamethonium 25 mg/kg; i.v.) produced equivalent cardiovascular responses suggesting similar global sympathetic activity between groups. Interestingly, gene expression of the β1-adrenoceptor pathway in cardiac tissue was unchanged.Our results suggest that CIH increases cardiac contractility via β1-adrenoceptor dependent mechanisms prior to development of global sympathetic hyperactivity suggesting that positive cardiac inotropy contributes to the development of hypertension in CIH-exposed rats.

Keywords: Cardiac contractility; Hypertension; Intermittent hypoxia; Obstructive sleep apnea; β1-adrenoceptor.

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