Hypertension III: Flow-Induced Vascular Remodeling

Re^2: Flow-induced remodeling and flow-induced vasodilatation

Joseph L. Unthank

On Thu Dec 10, Russell L. Prewitt wrote
>On Thu Dec 10, Jo De Mey wrote
>>Dear Dr Prewitt,

>>In your introduction you suggest a direct relationship between between endothelium-dependent flow-induced vasodilatation and flow-induced remodeling. I wonder what the direct experimental proof for this may be.
>>1. To my knowledge endothelium-dependency has only been demonstrated for the structural response of (juvenile) rabbit carotid arteries to blood flow reduction. What justifies to extrapolate this finding to arterioles and to chronic hyperperfusion?
>>2. Is there any evidence against a parallel (rather than a series) relationship between dilatation and outward remodeling. Outward remodeling may be an alternative pathway to normalise shear stress, rather than a consequence of dilatation. To put it differently, outward remodeling may develop in those conditions where dilatation is not (or no longer) capable of normalizing of shear stress.

>Dear Dr. DeMey,
>   You are correct that the only direct evidence linking the structural response of an artery to the endothelium is that of Langille on rabbit carotid arteries.  However, the sensing of shear stress by endothelial cells is well established and has been demonstrated in isolated resistance arteries by Koler.  Thus the endothelial cells are responsible for the vasodilation when blood flow and shear stress are increased.  Under normal conditions, an artery has resting tone which is reduced when flow increases through this endothelial-dependent mechanism.  If flow returns to resting levels, the diameter also returns.  If flow is chronically elevated, however, the maintained vasodilation leads to a growth response of both lumen and wall thickness.  So I think we are in agreement that outward remodeling occurs in conditions where dilatation can no longer normalize shear stress.  

Dear Drs. DeMey and Prewitt,

I would like to comment regarding endothelial dependency for structural remodeling associated with hyperfusion in the microcirculation.  First I would like to clarify that evidence does exist that an intact endothelium is required for luminal expansion and wall remodeling associated with elevated flow in large conduit arteries.  Two studies from Masuda's group demonstrate this.  The references are given below:

Masuda, H., K. Kawamura, T. Sugiyama, and A. Kamiya. Effects of endothelial denudation in flow-induced arterial dilatation.  Front.Med.Biol.Eng. 5: 57-62, 1993.

Tohda, K., H. Masuda, K. Kawamura, and T. Shozawa. Difference in dilatation between endothelium-preserved and - desquamated segments in the flow-loaded rat common carotid artery.  Arterioscler.Thromb. 12: 519-528, 1992.

In addition, as you know, shear modulates the expression of numerous growth modulators in cultured endothelial cells.  You are correct that endothelial dependence for structural alterations in hyperfused microvessels does not exist (to my knowledge).  But given the studies in large arteries and cultured endothelial cells, I wonder what evidence leads you to question whether the endothelium is required for shear-mediated luminal expansion and remodeling in hyper-perfused microvessels.  I would be most interested in your reasoning.  While our data is not yet published, the presentation by Tuttle in this symposium suggests that structural alterations in hyper-perfused small resistance vessels is very significantly suppressed in animals characterized with endothelial dysfunction (mature and hypertensive animals).



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