Invited Symposium: Hypertension III: Flow-Induced Vascular Remodeling
Discussion and Conclusion
THE ORCHIDECTOMY MODEL OF DECREASED BLOOD FLOW:
NORMAL MICROVASCULAR DEVELOPMENT:
The mechanism for the proliferation of precapillary arterioles during normal growth may be a metabolically related stimulus for angiogenesis. As the muscle grows, the capillaries become incapable of supplying enough oxygen and areas of hypoxia develop. This stimulates the growth of new capillaries, possibly through the release of angiogenic factors, such as basic fibroblast growth factor or adenosine. Capillaries form by budding from existing capillaries which in turn enlarge and take on a smooth muscle coat to form small arterioles.
As more capillaries develop and flow increases, the larger arterioles may be stimulated to grow by an endothelial mediated mechanism, either release of growth factors locally, or through chronic vasodilation. Although it may be possible for growth factors to diffuse from the venules to the larger arterioles, a more likely hypothesis is that growth factors act as paracrine or autocrine substances rather than circulating hormones. Alternatively, an increase in wall stress would result from vasodilation and this may be the stimulus for local growth of the arteriolar wall.
ALTERATIONS FOLLOWING ORCHIDECTOMY:
The inhibition of vascular growth was also evident in the number of 4A's per 3A, which did not increase following orchidectomy (Fig. 4). These results could be explained by decreased concentrations of metabolic growth factors resulting from reduced metabolic activity of the cremaster. Initiators of arteriolar proliferation on the control side, such as hypoxia, were not present following orchidectomy. In spite of this inhibition of growth, arteriolar density (Fig. 7) was greater after orchidectomy than in the contralateral cremaster, because skeletal muscle growth is primarily responsible for the reduction in arteriolar density. Growth of the muscle is also responsible for the extension of the arcading network and thus the total length of 2As was also reduced (Fig. 4).
One hypothesis for the ability of blood flow to be sensed by the vascular wall and initiate structural changes is through the effect of shear stress on the endothelium (2,3). Consistent with this hypothesis, the bottom panel of Figure 2 shows that the diameter of the 1A was adjusted so that the shear rate at the wall was nearly the same regardless of the flow rate. Shear stress is dependent upon the shear rate and viscosity of the blood, which in turn is dependent on the hematocrit. Hematocrit decreases with decreasing vessel diameter, but Jendrucko and Lee (9) showed that the hematocrit in a 116 lm glass tube was reduced only 10% below the value of the feed reservoir hematocrit. In vivo, Lipowsky et al. (10) found that the hematocrit in a 60 lm arteriole was about 80% of that of systemic. In the present experiment, the 1A diameters in the control and orchidectomy sides were 138 lm and 103 lm respectively. It is therefore likely that the 1A hematocrit in both cremasters was similar and close to the systemic hematocrit. Thus, it can be assumed that the shear stress is also similar in the orchidectomy and control 1A's. This means that the arterioles accommodated themselves to the changes in flow in a manner consistent with maintaining constant shear stress. This is in agreement with several investigations that suggest that mean shear stress is the key parameter determining the size and growth of the arterial lumen (2,3).
In conclusion, these experiments show that arteriolar development during maturation in skeletal muscle primarily consists of increases in length, diameter, and wall mass of vessels already present in the younger animal. Only precapillary arterioles increase in number to supply the additional capillaries which also develop with age. Unilateral orchidectomy inhibited the growth of the arteriolar bed, including the formation of new precapillary arterioles. Flow-induced shear stress and/or local changes in growth factors are suggested as possible mechanisms mediating the alterations.
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|Wang, DH.; Prewitt, RL.; (1998). Microvascular Adaptations to Reduced Blood Flow: Introduction of a New Model. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/prewitt/wang0894/index.html|
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