Genetic background affects cardiovascular responses to obstructive and simulated apnea.
We have recently demonstrated that genetic background significantly impacts the blood pressure and heart rate response to hypoxia (Campen MJ, Tagaito Y, Li J, Balbir A, Tankersley CG, Smith P, Schwartz A, and O'Donnell CP. Physiol Genomics 20: 15-20, 2005). Because hypoxia is considered a mediator of the acute and chronic cardiovascular complications of obstructive sleep apnea, we investigated whether genetic factors also influence the cardiovascular response to experimentally induced obstructive apnea (OA) and simulated apnea (SA). In three strains of inbred mice (C57BL/6J, DBA/2J, and FVB/J) anesthetized with urethane (1.2 g/kg), apnea was induced at end-expiration for 5- and 10-s periods in spontaneously breathing (OA) and mechanically ventilated (SA; pancuronium, 0.2 mg/kg bolus + 0.003 mg.kg(-1).min(-1)) animals before and after administration of an autonomic ganglionic blocker (hexamethonium, 20 mg/kg). In contrast to our previous findings with hypoxia, OA produced a marked hypertensive response in all three strains. However, strain impacted on the degree of bradycardia during OA, which was large in C57BL/6J and FVB/J mice and effectively absent in DBA/2J mice. In C57BL/6J but not FVB/J mice, the bradycardia was abolished with SA under mechanical ventilation. Cardiovascular responses to SA in all strains were eliminated by autonomic blockade. These data show that 1) DBA/2J mice, in contrast to the previous demonstration of marked bradycardia during hypoxia, unexpectedly do not produce bradycardia during apnea; 2) C57BL/6J mice exhibit a bradycardia that is dependent on input from thoracic afferents; and 3) FVB/J mice exhibit a bradycardia despite the loss of thoracic afferent input, consistent with a potent pressure response eliciting a baroreceptor-mediated bradycardia. Thus genetic background can affect both the pattern and magnitude of the cardiovascular response to apnea.
Iiyori
Nao
N
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Shirahata
Machiko
M
O'Donnell
Christopher P
CP
D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D008811:Mice, Inbred DBA / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000235:genetics / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000235:genetics* / Q000503:physiopathology*; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000503:physiopathology