Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice

Abstract

Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis. The results demonstrate that vasoconstriction elicited through a voltage-gated Ca(2+) mechanism (30-80 mM KCl) and thromboxane A2 receptors (10(-8) - 3 × 10(-5) M U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase activity (1 μM Y27632) abolished group differences in U46619-evoked contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10 μM, 2 μM U46619 preconstriction) was virtually absent in cerebral arteries from SF mice. The pressure-diameter relation was lower in arteries from SF mice relative to that in HC mice, which was not related to differences in the extracellular matrix protein elastin or collagen content or the elastin/collagen ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross-sectional area of unpressurized basilar arteries were not different among groups. These results suggest that the microgravity-induced attenuation of both vasoconstrictor and vasodilator properties may limit the range of vascular control of cerebral perfusion or impair the distribution of brain blood flow during periods of stress.

Keywords: brain blood flow; endothelium-dependent vasodilation; microgravity; vasoconstriction.

Fig. 1.

Effects of spaceflight on contractile responses to KCl in basilar arteries from habitat control (HC), vivarium control (VC), and 30-d Bion-M1 spaceflight (SF) mice. A: KCl concentration-active tension relations of basilar arteries. B: responses to different concentrations of KCl in percentage from 80 mM KCl response. Values are means ± SE; n = number of animals studied. *P < 0.05 between groups.

Fig. 2.

Effects of spaceflight on contractile responses to thromboxane receptor agonist U46619 in basilar arteries from HC, VC, and 30-d Bion-M1 SF mice. A: concentration-active tension relations of basilar arteries to U46619. B: concentration-response relations in the presence of Rho-kinase inhibitor Y27632 (1 μM). Inhibition of Rho-kinase led to significant reduction of contractile responses and eliminated the between-group differences. Values are means ± SE; n = number of animals studied. *P < 0.05 between groups.

Fig. 3.

Maximum relaxation responses of basilar arteries from HC, VC, and 30-day Bion-M1 SF mice to endothelium stimulation with 10 μM acetylcholine. The responses to acetylcholine are given as the percent relaxation of the 2 μM U46619-induced preconstriction. Values are means ± SE; n = number of animals studied. *P < 0.05 vs. spaceflight group.

Fig. 4.

Passive pressure-diameter responses to increases in transmural pressure in basilar arteries from HC, VC, and 30-day Bion-M1 SF mice. Values are means ± SE; n = number of animals studied. ^†P = 0.076 between SF and HC groups.

Fig. 5.

Effects of spaceflight on basilar artery extracellular matrix proteins: elastin (A), collagen (B), and the elastin/collagen ratio (C). Values are means ± SE; n = number of animals studied. *P < 0.05 vs. spaceflight group.