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Am J Physiol Regul Integr Comp Physiol 294: R1577-R1585, 2008. First published March 19, 2008; doi:10.1152/ajpregu.00084.2008
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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca2+ release mechanism

Patrick N. Colleran,1 Bradley J. Behnke,1,2 M. Keith Wilkerson,1 Anthony J. Donato,1 and Michael D. Delp1,3

1Department of Health and Kinesiology, Texas A&M University, College Station, Texas; 2Division of Exercise Physiology and the Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, West Virginia; and 3Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida

Submitted 6 February 2008 ; accepted in final form 17 March 2008

Previous work has shown that orthostatic hypotension associated with cardiovascular deconditioning results from inadequate peripheral vasoconstriction. We used the hindlimb-unloaded (HU) rat in this study as a model to induce cardiovascular deconditioning. The purpose of this study was to test the hypothesis that 14 days of HU diminishes vasoconstrictor responsiveness of mesenteric resistance arteries. Mesenteric resistance arteries from control (n = 43) and HU (n = 44) rats were isolated, cannulated, and pressurized to 108 cm H2O for in vitro experimentation. Myogenic (intralumenal pressure ranging from 30 to 180 cm H2O), KCl (2–100 mM), norepinephrine (NE, 10–9–10–4 M) and caffeine (1–20 mM) induced vasoconstriction, as well as the temporal dynamics of vasoconstriction to NE, were determined. The active myogenic and passive pressure responses were unaltered by HU when pressures remained within physiological range. However, vasoconstrictor responses to KCl, NE, and caffeine were diminished by HU, as well as the rate of constriction to NE (C, 14.8 ± 3.6 µm/s vs. HU 7.6 ± 1.8 µm/s). Expression of sarcoplasmic reticulum Ca2+ATPase 2 and ryanodine 3 receptor mRNA was unaffected by HU, while ryanodine 2 receptor mRNA and protein expression were diminished in mesenteric arteries from HU rats. These data suggest that HU-induced and microgravity-associated orthostatic intolerance may be due, in part, to an attenuated vasoconstrictor responsiveness of mesenteric resistance arteries resulting from a diminished ryanodine 2 receptor Ca2+ release mechanism.

hindlimb unloading; vasoconstrictor responsiveness



Address for reprint requests and other correspondence: M. D. Delp, Dept. of Applied Physiology & Kinesiology, Univ. of Florida, Gaineseville, FL 32611 (e-mail: mdelp{at}ufl.edu)







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