title: Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism.
abstract: Elevations in arterial pressure associated with hypertension, microgravity, and prolonged bed rest alter cerebrovascular autoregulation in humans. Using head-down tail suspension (HDT) in rats to induce cephalic fluid shifts and elevate arterial pressure, this study tested the hypothesis that 2-wk HDT enhances cerebral artery vasoconstriction and that an enhanced vasoconstriction described in vitro will alter regional cerebral blood flow (CBF) and vascular resistance (CVR) during standing and head-up tilt. To test this hypothesis, basal tone and vasoconstrictor responses to increases in transmural pressure, shear stress, and K(+) 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 N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and with endothelium removal. Endothelial NOS (eNOS) mRNA and protein expression levels were measured by RT-PCR and immunoblot, respectively. Regional CBF and CVR were determined with a radiolabeled tracer technique and quantitative autoradiography. Basal tone and all vasoconstrictor responses were greater in MCAs from HDT rats. L-NAME and endothelium removal abolished these differences between groups, and HDT was associated with lower levels of MCA eNOS protein. CBF in select regions was lower and CVR higher during standing and head-up tilt in HDT rats. These results indicate that chronic cephalic fluid shifts enhanced basal tone and vasoconstriction through alterations in the eNOS signaling mechanism. The functional consequence of these vascular alterations with HDT is regional elevations in CVR and corresponding reductions in cerebral perfusion.
authors.affiliation: Dept. of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA.
authors.forename: M Keith
authors.initials: MK
authors.lastname: Wilkerson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Elke M
authors.initials: EM
authors.lastname: Golding
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bryan
authors.forename: Aamir
authors.initials: A
authors.lastname: Amin
authors.forename: Emily
authors.initials: E
authors.lastname: Wilson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology; D006339:Heart Rate; D019417:Hindlimb Suspension / Q000009:adverse effects*; D007024:Hypotension, Orthostatic / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D018667:Tilt-Table Test; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011188:Potassium