Effect of Bed Rest on the Response of Human Limbs to Adrenergic Agonists

Open Access
Reitz, Nathan Robert
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • James Anthony Pawelczyk, Thesis Supervisor
  • Stephen Jacob Piazza, Honors Advisor
  • isoproterenol
  • phenylephrine
  • vasoconstriction
  • alpha adrenergic receptors
  • hydrostatic pressure gradient
Previous research by Pawelczyk and Levine identified a heterogeneous distribution of alpha adrenergic receptors between human limbs. The elevated hydrostatic pressure experienced by the legs upon standing is thought to be the main contributor toward this observed difference. This study aimed to determine whether exposure to bed rest deconditioning would ameliorate limb differences in the sensitivity to adrenergic agonists. It was hypothesized that the subsequent decrease in leg hydrostatic pressure, obtained through bed rest, would abolish the difference in α-adrenergic vasoconstriction between limbs. Methods: Eleven healthy subjects (10 men, 1 woman, mean age 24 ± 2 years) completed 18 days of bed rest with -6 head down tilt (HDT). Before and after bed rest, phenylephrine (five doses ranging from 0.025-0.8 µg •100 ml limb volume-1 • min-1) and isoproterenol (five doses ranging from 0.75-24.00 ng •100 ml limb volume-1 •min-1) were infused incrementally into the brachial and femoral arteries. Mean arterial pressure, heart rate, blood flow, vascular resistance and vascular conductance were measured at baseline and after each drug was infused for five minutes. Changes in limb blood flow were recorded using venous occlusion plethysmography. Results: Following bed rest, a significant increase in leg resistance was observed at the three highest doses of phenylephrine; however, no difference in the response to phenylephrine or isoproterenol infusion in the arm was noted following bed rest. Conclusion: Evidence from this study suggests that 18 days of bed does not normalize the responses of the limbs to infused adrenergic agonists. The increase in leg vasoconstriction post bed rest is likely due to a reduction in NO synthesis or an abnormality in the NO signaling pathway. This demonstrates that, in the short term, the hydrostatic pressure gradient experienced by the legs is not the key mediator of its adrenergic responsiveness.