NIH.R4/STS-80

Title of Study
Calcium Metabolism and Vascular Function in Rats after Space Flight


Science Discipline
Cardiovascular physiology


Investigator
Institute
David McCarron
Oregon Health Sciences University
 
 
Co-Investigator(s)
Institute
Daniel C. Hatton
Oregon Health Sciences University
Chantal Roulle
Oregon Health Sciences University
Hong Xue
Oregon Health Sciences University

Research Subjects
Rattus norvegicus (rat), spontaneously hypertensive
Flight: 14 Male


Ground Based Controls
Vivarium: 14, Asynchronous: 14


Key Flight Hardware
Ambient Temperature Recorder, Animal Enclosure Module


Objectives/Hypothesis
The inability of a vessel to increase resistance in the face of an orthostatic challenge is most likely associated with the problem of orthostatic intolerance. In animals that are exposed to simulated weightlessness, vascular contraction and regional blood flow is altered. The goal of this experiment was to investigate if similar changes in vascular contractility and cardiovascular function are associated with space flight.


Approach or Method
Twenty-one 1-day old male spontaneously hypertensive rats (SHR) were placed on either high calcium (2.0%) or low calcium (0.2%) diets. Indirect systolic blood pressure was measured at 5 and 7 weeks. The 7 rats from the low calcium diet group with the highest blood pressure, as well as the 7 rats from the high calcium group with the lowest pressure, were selected for the flight portion of the experiment. After landing, indirect systolic blood pressure and direct arterial blood pressure were determined. The animal was exsanguinated and the mesenteric vascular bed was collected. First, normalized media thickness and lumen diameter were determined. Then the vessel segment was set to its initial length and media thickness and axial length were measured. Next, the normalized length was measured with the vessel stretched to 90% of the diameter that it would have with an intraluminal pressure of 100 mmHg. Each vessel was then subjected first to a challenge with 100 mmol/l KCl three times and then to a challenge with 100 mmol/l KCl plus 10 μmol/l norepinephrine twice and its contractile response was measured.


Results
Anesthetic conditions were found to be associated with differences in blood pressure between flight and control animals. The flight groups' vascular contraction was found to be attenuated and relaxation to acetylcholine was diminished. However, there was no difference in relaxation due to sodium nitroprusside between the 2 groups. Analysis suggests an alteration in endothelial function that may be associated with increased synthesis and release of nitric oxide. Overall, results point to the hypothesis that the problem of increasing vascular resistance in the mesenteric vascular bed is due to the animals' inability to divert blood flow from the viscera. Thus, decreased vessel responsiveness in visceral vascular beds may contribute to orthostatic intolerance.


Publications

Hatton, D.C. et al.: Calcium Metabolism and Cardiovascular Function After Spaceflight. Journal of Applied Physiology, vol. 92(1), Jan 2002, pp. 3-12.

Hatton, D.C. et al.: Blood Pressure and Mesenteric Resistance Arterial Function After Spaceflight. Journal of Applied Physiology, vol. 92(1), Jan 2002, pp. 13-17.