Submitted on August 1, 2005
Accepted on January 25, 2006
Endothelium-Dependent Vasodilation of Cerebral Arteries Is Altered With Simulated Microgravity Through Nitric Oxide Synthase and EDHF Mechanisms
Rhonda D Prisby1, Keith Wilkerson2, Elke M Sokoya3, Robert M Bryan3, Emily Wilson4, and Michael D Delp5*
1 Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
2 Pharmacology, University of Vermont College of Medicine, Burlington, United States
3 Department of Anesthesiology, Baylor College of Medicine, Houston, Texas, United States
4 Medical Physiology, Texas A&M University Health Sciences Center, College Station, Texas, United States
5 Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, United States; Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia, United States
* To whom correspondence should be addressed. E-mail: mdd{at}hlkn.tamu.edu.
Cephalic elevations in arterial pressure associated with microgravity and prolonged bedrest alter cerebrovascular autoregulation in humans. Using the head-down tail-suspended (HDT) rat to chronically induce headward fluid shifts and elevate cerebral artery pressure, previous work has likewise shown cerebral perfusion to be diminished. The purpose of this study was to test the hypothesis that 2 wk HDT reduces cerebral artery vasodilation. To test this hypothesis, dose-response relations for endothelium-dependent (2-methylthioadenosine triphosphate [2-MeS-ATP] and bradykinin) and endothelium-independent (nitroprusside) vasodilation were determined in vitro in middle cerebral arteries (MCAs) from HDT and control rats. All in vitro measurements were done in the presence and absence of the nitric oxide synthase (NOS) inhibitor L-NAME (10-5 M) and cyclooxygenase inhibitor indomethacin (10-5 M). MCA caveolin-1 protein content was measured using immunoblot analysis. Endothelium-dependent vasodilation to 2-MeS-ATP and bradykinin were both lower in MCAs from HDT rats. These lower vasodilator responses were abolished with L-NAME, but were unaffected by indomethacin. In addition, HDT was associated with lower levels of MCA caveolin-1 protein. Endothelium-independent vasodilation was not altered by HDT. These results indicate that chronic cephalic fluid shifts diminish endothelium-dependent vasodilation through alterations in the eNOS signaling mechanism. Such decrements in endothelium-dependent vasodilation of cerebral arteries could contribute to the elevations in cerebral vascular resistance and reductions in cerebral perfusion that occur following conditions of simulated microgravity in HDT rats.
