FLI. Erythrocyte: force transducer. Mechanisms of blood pressure regulation in hypertension studied by Laser based EMFA technique. Shamci Monajembashi. Greulich Lab. Hemodynamic forces in vivo. Hypertension (high blood pressure): The endemic disease No.1 and a normal aging process.
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Mechanisms of blood pressure regulation in hypertension studied by Laser based EMFA technique
Hemodynamic forces in vivo
Hypertension (high blood pressure):
The endemic disease No.1 and a normal aging process
Endothelial nitric oxide (eNO) is produced in cells of the inner lining (intima) of blood vessels, diffuses to the smooth muscle cells (SMCs) of the media, where it causes relaxation of SMCs.
Substances acting on or prolonging this process are candidates for blood pressure relaxing drugs (for example VIAGRA).
So far, principally shear stress and cyclic stretch are used for studies on the response of cells to hemodynamic forces. However, little is reported about the response of endothelial cells to high vertical pressure in a few seconds.
The laser technique: Simulation of blood pressure by
EMFA (Erythrocyte Mediated Force Application)
Principle of EMFA
Fixed erythrocyte which is attached on the surface of endothelial cell, acts as a handle for optical tweezers to deform the cell.
HUVEC (Human Umbilical VeinEndothelial)Cells react by dramatic morphology changes after pressurizing
Laser power: 460 mW for 6 sec;Total observation time: 27 min.
Cell retraction changed after 6 min and lasted for 6 min (B-C).
Cell recovered after 18 min (D).
Laser power: 460 mW for 6 sec (B); Total observation time: 48 min.
Relaxation started ca. 6 min after EMFA pressure and lasted for ca. 41 min (C-F).
Stretch-activated ion channels are involved in the orienting response of endothelial cells (ECs) to pressure, e.g. pressure-induced morphological response of ECs is dependent on the external Ca++
Ca and NO correlate
Effect of calcium antagonists on endothelial nitric oxide bioavailibility
Calcium antagonists (CAs) are important drugs for the treatment of hypertension.
Amlodipine-stimulated NO release in HUVECs after EMFA:
A: typical changes of NO concentration after EMFA without Amlodipine,
B-C: prolonged NO release in present of Amlodipine after EMFA,
D: reduction of Amlodipine after 19 hours.