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01-09-2010 | Original Article

Early changes in vasoreactivity after simulated microgravity are due to an upregulation of the endothelium-dependent nitric oxide/cGMP pathway

Authors: Anthony R. White, Sungwoo Ryoo, Lukasz Bugaj, David O. Attarzadeh, Srikanth Thiyagarajan, Kexun Chen, Sarah Attwater, Bryce Abbot, Dechun Li, Hunter C. Champion, Artin A. Shoukas, Daniel Nyhan, Joshua M. Hare, Dan E. Berkowitz, Eric C. Tuday

Published in: European Journal of Applied Physiology | Issue 2/2010

Abstract

Emerging evidence suggests that nitric oxide (NO) plays a pivotal role in the mechanism of vascular hyporesponsiveness contributing to microgravity-induced orthostatic intolerance. The cellular and enzymatic source of the NO, however, remains controversial. In addition, the time course of the endothelial-dependent contribution remains unstudied. We tested the hypotheses that the change in vasoresponsiveness seen in acute (3-day) hindlimb unweighted (HLU) animals is due to an endothelium-dependent mechanism and that endothelial-dependent attenuation in vasoreactivity is due to endothelial nitric oxide synthase (NOS-3) dependent activation. Vasoreactivity was investigated in rat aortic rings following acute HLU treatment. Dose responsiveness to norepinepherine (NE) was depressed after 3-day HLU [1,338 ± 54 vs. 2,325 ± 58 mg at max (NE), HLU vs. C, P < 0.001]. However, removal of the endothelium restored the vascular contractility to that of C. In addition, 1H-oxadiazole quinoxalin-1-one (ODQ), a soluble guanylyl cyclase inhibitor, restored the reduced vasoconstrictor responses to phenylephrine (PE) seen in 3-day HLU rings (1.30 ± 0.10 vs. 0.53 ± 0.07 g, HLU + ODQ vs. HLU, P = 0.0001). Ca⁺ dependent nitric oxide synthase (NOS) activity was increased, as was vascular NO products as a result of HLU. While NOS-3 expression was not increased in HLU rats, phosphorylation of NOS-3 at serine-1177 (an activator of NOS-3) was increased while phosphorylation of serine-495 (an inactivator of NOS-3) was decreased. These findings demonstrate that changes in vasoresponsiveness in the acute HLU model of microgravity are due to an upregulation of the endothelial-dependent NO/cGMP pathway through NOS phosphorylation.

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Title: Early changes in vasoreactivity after simulated microgravity are due to an upregulation of the endothelium-dependent nitric oxide/cGMP pathway
Authors: Anthony R. White
Sungwoo Ryoo
Lukasz Bugaj
David O. Attarzadeh
Srikanth Thiyagarajan
Kexun Chen
Sarah Attwater
Bryce Abbot
Dechun Li
Hunter C. Champion
Artin A. Shoukas
Daniel Nyhan
Joshua M. Hare
Dan E. Berkowitz
Eric C. Tuday
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: European Journal of Applied Physiology / Issue 2/2010
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-010-1514-7

At a glance: The STEP trials

Springer Medicine

Early changes in vasoreactivity after simulated microgravity are due to an upregulation of the endothelium-dependent nitric oxide/cGMP pathway

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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