Angiogenesis in Mesenteric Microvascular Networks from Spontaneously Hypertensive Versus Normotensive Rats

Abstract

Elevated blood pressure during hypertension has been associated with microvascular rarefaction defined by loss of microvessels. However, whether rarefaction is a result of impaired angiogenesis remains unclear. The objective of this study was to compare angiogenesis across the time course of mesenteric microvascular network remodeling in adult spontaneously hypertensive versus normotensive rats. Angiogenic responses in 15–16-week-old SHR and Wistar rats at 0, 3, 5, 10 or 25 days post 20 minute exteriorization of the mesentery were quantified. Consistent with the phenomenon of rarefaction, vascularized area in unstimulated SHR was decreased compared to Wistar. By 25 days, SHR vascular area had increased to the Wistar level and vascular length density and capillary sprouting were comparable. At 3 and 5 days, SHR and Wistar tissues displayed an increase in the capillary sprouting and vascular density relative to their unstimulated controls. At 10 days, capillary sprouting in the SHR remained elevated. The percent change in vascular density was elevated in the SHR compared to the Wistar group at 3 and 5 days and by 25 days the rate of change was more negative. Our results suggest that SHR networks undergo an increased rate of growth followed by an increased rate of pruning.

Rat Mesentery Exteriorization: A Model for Investigating the Cellular Dynamics Involved in Angiogenesis

“…While the unknown mechanisms remain a major critique of this model, its reproducibility and simplicity make it attractive for identifying cellular dynamics involved in the inherently complex capillary sprouting process. The reproducibility of the model is supported by comparable angiogenic metrics over the time course of microvascular network growth across multiple rat strains (male Wistar and female Sprague-Dawley) in previously published studies from our laboratory 10,12 . Since, the majority of adult rat mesenteric tissues are vascularized, the model also allows for multiple tissues to be examined per animal.…”

“…In our laboratory, we have used this model to identify pericyte phenotypic changes over the time course of the angiogenic response 10 and to assess the angiogenic potential during pathological conditions, such as hypertension 12 .…”

“…Tissues can generally now be labeled according to instructions per antibody for immunohistochemistry. Given our interest in identifying the roles of vascular pericytes during angiogenesis, our laboratory commonly labels for endothelial and perivascular cells 10,12,13 . Useful labels to identify endothelial cells along the hierarchy of the microvascular networks are an anti-PECAM antibody or BSI-lectin.…”

Relationships Between Lymphangiogenesis and Angiogenesis During Inflammation in Rat Mesentery Microvascular Networks

“…7,12,15 Capillary sprouting was evaluated by quantifying the number of blind-ended capillary segments per vessel type. For the blood microvasculature in the mesentery, such blind-ended vessels are associated with endothelial cell proliferation.…”

Impact of Comorbidities on Acute Injury and Recovery in Preclinical Stroke Research: Focus on Hypertension and Diabetes

“…In addition, widespread astrogliosis, inflammation, and blood brain barrier (BBB) dysfunction occurs in middle age and has been implicated in the development of cognitive impairment in this model [15]. Microvascular rarefaction in numerous vascular beds, in both rat and human hypertension has been reported [16], but increased angiogenesis has also been reported in SHRs [17, 18], in response to some stimuli. It is likely that the specific tissue microenvironment contributes to the pro- or anti-angiogenic state created after injury.…”