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Summary

Principal Investigator: Jonathan P Alberding
Abstract: DESCRIPTION: (provided by applicant): Study of Filtration Under Pulsatile Pressure in Large Arteries. Measuring filtration in large arteries undergoing pulsatile pressure is rarely attempted due to the difficulty of distinguishing effects of arterial distension from those of true filtration. Accurate measurements of filtration are necessary to evaluate convective lipoprotein deposition in large arteries. My preliminary results show that pulsatile pressure induces a transient increase in apparent filtration. However, this could be mediated by an increase in arterial distension. Optical Coherence Tomography now permits accurate measurements of vessel distension so that true filtration can be determined. Using this technique the effect of pulsatile pressure on arterial transport and mechanical properties will be evaluated. The aims are as follows: 1) To determine whether pulsatile pressure increases arterial hydraulic conductance or residual distension. 2) Observe whether the apparent increase in filtration occurs after a change in pulsatile pressure amplitude and/or frequency as well as at the onset of pulsatile pressure. 3) Use paired carotid arteries (one de-endothelialized) to measure the effects the endothelium has upon the response. 4) Observe the effects of pulsatile pressure on gaps in endothelial junctions (provided the observed filtration is found to be endothelial-mediated), using Silver Nitrate staining. 5) If apparent filtration is due to changes in arterial distension, rather than changes in hydraulic conductance: A) Use an eNOS inhibitor to see if distention is Nitric oxide dependent. B) Or use indomethacin and/or ibuprofen to see if the distension is dependent on release of vasodilators PGI2/PGE2 from smooth muscle cells and/or endothelial cells.
Funding Period: 2002-07-01 - 2004-06-30
more information: NIH RePORT