The purpose of this proposal is to determine whether the fluid shifts and reduced activity of postural muscles induced by microgravity similarly alter rodent arterial vessel structure and some key cellular signaling pathways: does space flight result in smooth muscle atrophy of skeletal muscle and mesenteric arteries.
The mesenteric and gastrocnemius muscle resistance arteries were isolated and placed in cold buffer solution at KSC. The arteries were then transported to the University of Florida where they were mounted on glass pipettes for in vitro experimentation. Wall thickness and lumen diameter were measured using video microscopy. The resistance arteries were further studied to determine physiological responses to vasoconstrictor agonists working through different mechanisms.
Results in the mesenteric and gastrocnemius muscle resistance arteries demonstrate that microgravity attenuates both the magnitude and the rapidity of vasoconstrictor responses to norepinephrine, a receptor-mediated vasoconstrictor mechanism, as well as to KCl, a non-receptor vasoconstrictor mechanism. Furthermore, vasoconstrictor responses to caffeine, an intracellular calcium-release mechanism through ryanodine receptors, were also attenuated in mesenteric resistance arteries after spaceflight. Analysis of mRNA expression of ryanodine receptors in mesenteric and gastrocnemius arteries demonstrated depressed expression in the flight animals relative to controls mice. These microgravity-induced changes in arterial vasoconstriction occurred in the absence of any gross structural changes in artery wall thickness or maximal interluminal diameter, or by any alterations in the passive mechanical properties of the vessels, as indicated by an unaltered passive pressure-diameter response.