Microvascular Network Restructuring Associated with MMP Inhibition in Spontaneously Hypertensive Rats

Abstract

Recently, we have shown that MMP inhibition via doxcycyline treatment normalizes blood pressure and attenuates cell dysfunction, i.e. insulin resistance, in adult spontaneously hypertensive (SHR) rats. The objective of this work was to determine whether MMP inhibition leading to blood pressure normalization in hypertensive animals is associated with microvascular network structural alterations. Age matched (14–16 wks) SHR and Wistar‐Kyoto (WKY) rats were administered normal drinking water with and without doxycycline (5.4 mg/kg/d) for 12 weeks. Mesenteric tissues were harvested from 3–5 animals per experimental group and immunolabeled for CD31. Intact microvascular networks were compared based on 3 metrics: vascular area per total tissue area, vessel length per vascular area, and capillary sprouts (blind ended vessels) per vascular area. Microvascular networks from control SHR animals exhibited decreased vascular area per tissue area (P=0.030) and increased vessel length per vascular area (P=0.039) compared to the control WKY group. Networks from the doxycycline treated‐SHR group did not exhibit similar differences. Additionally, doxycylcline treatment served to decrease capillary sprouting per vascular area in SHR animals (P=0.039). These results suggest that microvascular network patterning is linked to MMP activity in adult spontaneously hypertensive rats. Supported by NIH‐HL10881.