Chronic intermittent hypoxia increases left ventricular contractility in C57BL/6J mice.
Intermittent hypoxia (IH) commonly occurs in patients with obstructive sleep apnea and can cause a wide range of pathology, including reduced left ventricular (LV) ejection fraction in rats as determined by echocardiography, in rodent models. We utilized echocardiography and pressure-volume (PV) loop analyses to determine whether LV contractility was decreased in inbred C57BL/6J mice exposed to IH and whether blockade of beta-adrenergic receptors modified the response to hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir inspired O(2) 5-6% at 60 cycles/h for 12 h during the light period) or intermittent air (IA) as control. A second group of animals were exposed to the same regimen of IH or IA, but in the presence of nonspecific beta-blockade with propranolol. Cardiac function was assessed by echocardiography and PV loop analyses, and mRNA and protein expression in ventricular homogenates was determined. Contrary to our expectations, we found with PV loop analyses that LV ejection fraction (63.4 +/- 3.5 vs. 50.5 +/- 2.6%, P = 0.015) and other measures of LV contractility were increased in IH-exposed animals compared with IA controls. There were no changes in contractile proteins, atrial natriuretic peptide levels, LV posterior wall thickness, or heart weight with IH exposure. However, cAMP levels were elevated after IH, and propranolol administration attenuated the increase in LV contractility induced by IH exposure. We conclude that, contrary to our hypothesis, 4 wk of IH exposure in C57BL/6J mice causes an increase in LV contractility that occurs independent of ventricular hypertrophy and is, in part, mediated by activation of cardiac beta-adrenergic pathways.
Naghshin
Jahan
J
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
McGaffin
Kenneth R
KR
Witham
William G
WG
Mathier
Michael A
MA
Romano
Lia C
LC
Smith
Steven H
SH
Janczewski
Andrejz M
AM
Kirk
Jonathan A
JA
Shroff
Sanjeev G
SG
O'Donnell
Christopher P
CP
D000319:Adrenergic beta-Antagonists; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D004452:Echocardiography; D015870:Gene Expression / Q000502:physiology; D000860:Hypoxia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D017931:DNA Primers; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000242:Cyclic AMP