Berkowitz DE, Mo Z, Winters B, Nyhan D, Shoukas A.
Anesthesiology. 1999 Sep; 91: A647.
Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
INTRODUCTION: Orthostatic intolerance with resultant postural syncope and tachycardia is a significant problem following prolonged bedrest or exposure to microgravity. The mechanism of attenuated blood pressure response to an orthostatic challenge is incompletely understood. Normal or enhanced norepinephrine (NE) responses suggest that the abnormality may be at the level of the vasculature. We have recently demonstrated impaired vasoreactivity in aortic rings in a rat model of microgravity. We now present evidence that microvascular responses to adrenergic agonists are likewise impaired. METHODS: In vitro vascular reactivity to PE was tested in mesenteric microvessels of control and hind limb unweighted (HLU) rats. Rats were HLU for 14-21 days (an accepted ground based model of cardiovascular deconditioning). Approximately 250 um mesenteric vessels were cannulated at both ends with glass micropipettes. The arteries were maintained in a no-flow state and held at a constant transluminal pressure of 40mmHg. The chamber was superfused with KR solution, placed on the stage of an inverted microscope. The vessel image was projected onto a video monitor and intraluminal diameter was determined continuously by a video dimension analyzer Dose-response curves to PE, (10-4 to 10-9) were generated in 1/2 log order concentration and responses recorded using a MacLab system and the software. RESULTS: Microvessel responses to PE were markedly attenuated in HLU animals (log EC50 -5.2 +/- 0.07 vs.-6.0 +/- 0.12, p<0.05, n=4) CONCLUSIONS: Impaired microvascular responses in the HLU rats suggests rats impairment of end organ alpha-1AR signaling in the microvasculature. This may represent an important mechanims of orthostatic intolerance associated with prolonged bedrest and microgravity associated cardiovascular deconditioning. This in turn may provide insights into novel countermeasures which will sustain blood pressure and cardiac output following cardiovascular deconditioning, or prevent its development.
Publication Types:
Keywords:
- Animals
- Arteries
- Bed Rest
- Blood Pressure
- Cardiovascular Deconditioning
- Hindlimb
- Hindlimb Suspension
- In Vitro
- Norepinephrine
- Rats
- Rats, Sprague-Dawley
- Weightlessness
- Weightlessness Simulation
- NASA Discipline Cardiopulmonary
- Non-NASA Center
Other ID:
UI: 102184893
From Meeting Abstracts