Chapter 12. Structure of microvascular networks in genetic hypertension

• Published in: Methods in enzymology Vol. 444; p. 271
• Main Authors: Murfee, Walter L, Schmid-Schönbein, Geert W
• Format: Journal Article
• Language: English
• Published: United States 2008
• Subjects: Animals; Genetic Predisposition to Disease - genetics; Humans; Hypertension - genetics; Hypertension - physiopathology; Immunohistochemistry; Male; Microvessels - metabolism; Microvessels - physiopathology; Neovascularization, Pathologic; Rats
• ISSN: 1557-7988
• DOI: 10.1016/S0076-6879(08)02812-7

Microvascular rarefaction, defined by a loss of terminal arterioles, small venules, and/or capillaries, is a common characteristic of the hypertension syndrome. While rarefaction has been associated with vessel-specific free radical production, deficient leukocyte adhesion, and cellular apoptosis, the relationships of rarefaction with structural alterations at the network and cellular level remain largely unexplored. The objective of this study was to examine the architecture and perivascular cell phenotypes along microvascular networks in hypertensive versus normotensive controls in the context of imbalanced angiogenesis. Mesenteric tissues from age-matched adult male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were harvested and immunolabeled for PECAM and neuron-glia antigen 2 (NG2). Evaluation of intact rat mesenteric microvascular networks rats suggests that network alterations associated with hypertension are more complex than just a loss of vessels. Typical SHR versus WKY networks demonstrate a reduced branching architecture marked by more proximal arteriole/venous anastomoses and an absence of NG2 labeling along arterioles. Although less frequent, larger SHR microvascular networks display regions of dramatically increased vascular density. SHR and WKY lymphatic networks demonstrate increased vessel diameters and vascular density compared to networks in normotensive Wistar rats (the strain from which both the SHR and WKY originated). These observations provide a rationale for investigating the presence of local angiogenic factors and response of microvascular networks to therapies aimed at reversing rarefaction in genetic hypertension.