title: Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice.
abstract: Whether myocardial contractile impairment contributes to orthostatic intolerance (OI) is controversial. Accordingly, we used transient bilateral carotid occlusion (TBCO) to compare the in vivo pressor, chronotropic, and inotropic responses (parts 1 and 2) to open-loop selective carotid baroreceptor unloading in anesthetized mice. In part 3, in vitro myocyte responses to isoproterenol in mice exposed to hindlimb unweighting (HLU) for approximately 2 wk were determined. Heart rate (HR) and mean arterial pressure (MAP) responses to TBCO were measured. In control mice, TBCO increased HR (15 +/- 2 beats/min, P < 0.05) and MAP (17 +/- 2 mmHg, P < 0.05). These responses were markedly potentiated in denervated control (DC) mice, in which the aortic depressor nerve and sympathetic trunk were sectioned before measurement. Baroreflex responses to TBCO were eliminated by blockade with hexamethonium bromide (10 microg/kg). In HLU (denervated) mice, HR and MAP responses were reduced approximately 70% compared with DC mice. In part 2, myocardial contractile responses to TBCO were measured with a left ventricular micromanometer-conductance catheter. TBCO in DC mice increased the slope of the end-systolic pressure-volume relation (end-systolic elastance) by 86 +/- 13%. This inotropic response was attenuated (14 +/- 10%, P < 0.005) after HLU. In part 3, contractile responses to isoproterenol were impaired in myocytes isolated from HLU mice. In conclusion, selective carotid baroreceptor unloading stimulates HR, blood pressure, and myocardial contractility, and HLU attenuates each response. These findings have important implications for the management of OI in astronauts, the elderly, and individuals subjected to prolonged bed rest.
authors.affiliation: Department of Biomedical Engineering, Critical Care Medicine, Johns Hopkins Univ. School of Medicine, 600 N Wolfe St., Baltimore, MD 21287, USA.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Jung
authors.forename: Robert
authors.initials: R
authors.lastname: Harrison
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Lee
authors.forename: Jordan
authors.initials: J
authors.lastname: Genut
authors.forename: Daniel
authors.initials: D
authors.lastname: Nyhan
authors.forename: E M
authors.initials: EM
authors.lastname: Brooks-Asplund
authors.forename: Artin A
authors.initials: AA
authors.lastname: Shoukas
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
mesh_terms: D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000494:pharmacology; D016893:Carotid Stenosis / Q000503:physiopathology*; D006339:Heart Rate; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D018474:Weightlessness Simulation
chemical_list: D002316:Cardiotonic Agents; D007545:Isoproterenol