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Immunohistochemical identification of arteriolar development using markers of smooth muscle differentiation. Evidence that capillary arterialization proceeds from terminal arterioles

, : Immunohistochemical identification of arteriolar development using markers of smooth muscle differentiation. Evidence that capillary arterialization proceeds from terminal arterioles. Circulation Research 75(3): 520-527

Arteriolar growth is an important event in the adaptation of normal tissues as well as in important pathologies, but the site of origin of new arterioles remains unknown. The network pattern of arteriolar development in skeletal muscle was detected by use of a new immunohistochemical technique that is based on the observation that fully differentiated (mature) vascular smooth muscle (SM) cells express both SM alpha-actin and the two myosin heavy chains (MHCs) SM-1 and SM-2, whereas less differentiated (immature) vascular SM cells do not express MHC. The anterior gracilis muscle microvasculatures of 4- and 9-week-old Sprague-Dawley rats were labeled with monoclonal antibodies to SM alpha-actin and to SM MHC. Whole transverse arteriole networks were observed, and terminal arterioles, defined as terminal segments labeled with SM alpha-actin, were classified on the basis of the presence or absence of SM MHC. A significantly different percentage of terminal arteriolar endings per network without SM MHC was observed in the two groups (66.1 +- 17.3% for 4 weeks and 27.1 +- 18.5% for 9 weeks), suggesting that arteriolar development is more nearly complete in the older animals. Sparsely distributed capillaries exhibited thin extensions of SM alpha-actin that crossed collecting venules and joined similar extensions from an adjacent transverse arteriole, effectively forming the basis for new arcade arterioles. SM alpha-actin and SM MHC labeling in terminal arterioles was always continuous with upstream arterioles. The pattern of labeling provides evidence that arterialization proceeds along capillaries from the terminal arteriolar endings, as opposed to being initiated at random sites on the developing vasculature that are distal to the arterioles. The methods described herein provide a powerful means to assess how factors such as tissue hypoxia, growth factors, and hemodynamic stresses affect arteriolar development as well as remodeling.


PMID: 8062425

DOI: 10.1161/01.RES.75.3.520

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