Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice

Albert S. Jung, Robert Harrison, Kwang H. Lee, Jordan Genut, Daniel Nyhan, E. M. Brooks-Asplund, Artin A. Shoukas, Joshua Hare, Dan E. Berkowitz

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 ∼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 μg/kg). In HLU (denervated) mice, HR and MAP responses were reduced ∼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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number2 58-2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Weightlessness
Baroreflex
Hindlimb
Heart Rate
Orthostatic Intolerance
Arterial Pressure
Pressoreceptors
Isoproterenol
Muscle Cells
Astronauts
Blood Pressure
Hexamethonium
Bed Rest
Catheters

Keywords

  • Baroreflex
  • Cardiovascular deconditioning
  • Hindlimb unweighting
  • Microgravity
  • Mouse
  • Orthostatic hypotension

ASJC Scopus subject areas

  • Physiology

Cite this

Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice. / Jung, Albert S.; Harrison, Robert; Lee, Kwang H.; Genut, Jordan; Nyhan, Daniel; Brooks-Asplund, E. M.; Shoukas, Artin A.; Hare, Joshua; Berkowitz, Dan E.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 2 58-2, 01.08.2005.

Research output: Contribution to journalArticle

Jung, Albert S. ; Harrison, Robert ; Lee, Kwang H. ; Genut, Jordan ; Nyhan, Daniel ; Brooks-Asplund, E. M. ; Shoukas, Artin A. ; Hare, Joshua ; Berkowitz, Dan E. / Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 289, No. 2 58-2.
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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 ∼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 μg/kg). In HLU (denervated) mice, HR and MAP responses were reduced ∼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.",
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AU - Harrison, Robert

AU - Lee, Kwang H.

AU - Genut, Jordan

AU - Nyhan, Daniel

AU - Brooks-Asplund, E. M.

AU - Shoukas, Artin A.

AU - Hare, Joshua

AU - Berkowitz, Dan E.

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KW - Mouse

KW - Orthostatic hypotension

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