ROLE OF HEMODYNAMIC FORCES IN SMOOTH MUSCLE CELL CONTRACTION AND TRANSVASCULAR FILTRATION IN VIVO
Open Access
- Author:
- Kim, Min-ho
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 22, 2004
- Committee Members:
- Norman R Harris, Committee Chair/Co-Chair
Herbert Herling Lipowsky, Committee Member
Peter J Butler, Committee Member
Donna Hope Korzick, Committee Member
John Michael Tarbell, Committee Member - Keywords:
- shear stress
microvascular pressure
myogenic response
transvascular filtration
hydraulic conductivity
vascular smooth muscle cell
endothelial cell - Abstract:
- The vascular wall is continuously exposed to two hemodynamic forces imparted by blood flow: pressure and shear stress. Significant changes in hemodynamic forces can occur in many physiological and pathophysiological circumstances. Changes in vascular pressure and blood flow-induced shear stress can affect vascular endothelium and smooth muscle cells (SMCs) mechanically. When vascular pressure is increased, an increase in transvascular filtration is driven by a classical Starling mechanism. This increased transvascular filtration is expected to induce increases in shear stresses through the inter-endothelial cleft surfaces and SMCs. A main hypothesis of the current study is that transvascular filtration-induced shear stress might play important roles in endothelial barrier function and SMC contractions. To address this hypothesis, we investigated the effect of pressure-induced transvascular fluid flux on SMC contraction in vivo. We also investigated the effects of pressure and shear on endothelial barrier functions for water transport. In the current study performed in vivo and in excised arterioles, interstitial flow-induced shear stress through the vascular wall driven by transvascular filtration was hypothesized to be a mechanical factor that can play a role in the myogenic response in addition to the role of vascular stretch and wall tension. To address this hypothesis, we investigated the relationship between filtration rate (Jv) and the myogenic response by modifying plasma osmotic pressure to attenuate Jv during a step increase in hydrostatic pressure. The myogenic response was attenuated significantly when an osmotic solution of albumin, or albumin plus Ficoll, was infused into the bloodstream to decrease fluid filtration. Moreover, the same inhibition of myogenic tone was found in isolated, cannulated rat soleus muscle arterioles when filtration was osmotically attenuated by intravascular dextran. Taken together, these results are consistent with the hypothesis that shear stress on arteriolar smooth muscle, induced by transvascular fluid filtration, is a contributing factor that helps control myogenic tone. To understand the role of hemodynamic forces in regulating microvascular permeability, we have investigated effects of acute changes in shear and pressure on endothelial barrier function for water transport. In the study performed in the microvessels of the mesentery, we have obtained evidence that hydraulic conductivity might be regulated via a NO-dependent mechanism in response to acute change in shear rate. Additionally, the effect of sustained changes in pressure on hydraulic conductivity was also investigated using micro-perfusion technique. The substantial increase in hydraulic conductivity was observed following a pressure increase in both small arterioles and venules. It is likely that pressure-induced mechanical stimulus activates a biochemical response that can lead to increase in hydraulic conductivity in response to pressure change. Furthermore, our results suggested that an adaptive sealing effect induced by a step change in pressure also partially contributes to regulate endothelial barrier function. These findings support the idea that endothelial transport barrier responds actively to changes in hemodynamic forces in the microcirculation and regulate transport pathways for water through biological as well as mechanical mechanisms.