Effects of spaceflight and ground recovery on mesenteric artery and vein constrictor properties in mice

Abstract

Following exposure to microgravity, there is a reduced ability of astronauts to augment peripheral vascular resistance, often resulting in orthostatic hypotension. The purpose of this study was to test the hypothesis that mesenteric arteries and veins will exhibit diminished vasoconstrictor responses after spaceflight. Mesenteric arteries and veins from female mice flown on the Space Transportation System (STS)-131 (n=11), STS-133 (n=6), and STS-135 (n=3) shuttle missions and respective ground-based control mice (n=30) were isolated for in vitro experimentation. Vasoconstrictor responses were evoked in arteries via norepinephrine (NE), potassium chloride (KCl), and caffeine, and in veins through NE across a range of intraluminal pressures (2-12 cmH(2)O). Vasoconstriction to NE was also determined in mesenteric arteries at 1, 5, and 7 d postlanding. In arteries, maximal constriction to NE, KCl, and caffeine were reduced immediately following spaceflight and 1 d postflight. Spaceflight also reduced arterial ryanodine receptor-3 mRNA levels. In mesenteric veins, there was diminished constriction to NE after flight. The results indicate that the impaired vasoconstriction following spaceflight occurs through the ryanodine receptor-mediated intracellular Ca(2+) release mechanism. Such vascular changes in astronauts could compromise the maintenance of arterial pressure during orthostatic stress.

Figure 1.

A) NE dose-response relations of mesenteric arteries from GC and 15-d STS-131 SF mice. B) Mean response time and rate of constriction after exposure to 10⁻⁴ M NE in mesenteric arteries from GC and SF mice. Values are means ± se; n = number of animals studied. *P < 0.05 between groups.

Figure 2.

A) Potassium chloride dose-response relations of mesenteric arteries from GC and 15-d STS-131 SF mice. B) Active and passive diameter responses to changes in transmural pressure in mesenteric arteries from GC and 15-d STS-131 SF mice. Values are means ± se; n = number of animals studied. Active responses were different from passive responses within each group, but neither active nor passive diameter responses were different between vessels from GC and SF mice. *P < 0.05 between groups.

Figure 3.

A) Maximal vasoconstrictor response to 15 mM caffeine in mesenteric arteries from GC and 15-d STS-131 SF mice. B, C) Effects of spaceflight on RyR-2 (B) and RyR-3 (C) mRNA expression in mesenteric arteries from GC and 15-d STS-131 SF mice. Values are means ± se; n = number of animals studied. *P < 0.05, ^†P < 0.10 vs. GC.

Figure 4.

NE dose-response relations in mesenteric arteries from GC and 13-d STS-133 SF mice at R+1 d (A), R+5 d (B), and R+7 d (C) after return from flight. Values are means ± se; n = number of animals studied. *P < 0.05 between groups.

Figure 5.

A) NE dose-response relations in mesenteric veins from GC and 13-d STS-135 SF mice. B) Intraluminal pressure-diameter relations in mesenteric veins from GC and 13-d STS-135 SF mice following preincubation in 10⁻⁴ M NE. Values are means ± se; n = number of animals studied. *P < 0.05 between groups.