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 language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 289 |
| Issue number | 2 58-2 |
| DOIs | |
| State | Published - Aug 1 2005 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice
AU - Jung, Albert S.
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.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
KW - Baroreflex
KW - Cardiovascular deconditioning
KW - Hindlimb unweighting
KW - Microgravity
KW - Mouse
KW - Orthostatic hypotension
UR - http://www.scopus.com/inward/record.url?scp=23744445252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23744445252&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.01091.2004
DO - 10.1152/ajpheart.01091.2004
M3 - Article
C2 - 15778286
AN - SCOPUS:23744445252
VL - 289
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 2 58-2
ER -