Three days of chronic intermittent hypoxia is sufficient to induce β1‐adrenoceptor dependent increases in left ventricular contractility

Abstract

Chronic intermittent Hypoxia (CIH) is the primary pathological feature of obstructive sleep apnea, manifesting sympathetic nervous system hyperactivity and hypertension. Modest durations of CIH exposure have been shown to increase cardiac output that may contribute to the hypertensive state. Prolonged CIH exposures induce heart failure. We sought to determine if increases in cardiac work develop before the CIH‐induced hypertensive phenotype is established.Male Wistar rats were exposed to repetitive cycles of hypoxia (FiO2=0.05 nadir; 90 seconds) and normoxia (FiO2=0.21; 210 seconds) for eight hours per day for three days (CIH; n=6). Sham animals (n=7) were constantly exposed to room air and the same environmental cues. Assessment of cardiovascular parameters was performed under urethane anesthesia (1.5 g/kg i.p.). Data are presented as mean±SD (sham vs CIH) and were analysed using unpaired Student's t‐tests. P<0.05 was taken as significant.Systolic blood pressure (p=0.439), mean arterial pressure (p=0.267) and heart rate (p=0.149) were all unaffected by three days of CIH exposure. In addition, plasma adrenaline (p=0.294) and noradrenaline (p=0.155) concentrations were not elevated in CIH exposed animals compared with sham controls. However, at baseline, left ventricular contractility (dP/dtMAX) was significantly increased in CIH exposed animals compared with sham animals (12320 ± 2725 vs 15300 ± 2002 mmHg/s; p=0.025). Interestingly, β1‐adrenoceptor inhibition with atenolol (5 mg/kg; i.v.) provided greater inhibition of left ventricular contractility in CIH animals compared with sham animals (−4747 ± 2080 vs −7604 ± 1298 mmHg/s; p=0.014), reducing dP/dtMAX to equivalent levels. Systolic blood pressure (p=0.735) and heart rate (p=0.25) responses to atenolol were similar in sham and CIH animals. Sympathetic ganglion blockade with hexamethonium (25 mg/kg; i.v.) produced equivalent responses in CIH and sham animals for measured cardiovascular parameters (p>0.05).This study suggests that global sympathetic hyperactivity has not yet developed in this three‐day model of CIH, as evidenced by catecholamine concentrations, blood pressure and heart rate, which are equivalent with sham animals. Nevertheless, three days of CIH exposure is sufficient to increase cardiac work. We hypothesize that through this mechanism the heart drives development of the hypertensive phenotype in the early stages of CIH, as opposed to sympathetically‐mediated peripheral vasoconstriction.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.