Reversal of endothelial apoptosis and capillary rarefaction by chronic MMP inhibition. TUNEL labeling of apoptotic endothelial cells, capillaries with intracellular domain of VEGFR-2 labeling in the microcirculation of the rat heart, and capillary networks in the cremaster muscle microcirculation with fluorescent lectin labeling. a The number of TUNEL-positive endothelial cells is significantly higher in SHR cardiac arteries. After chronic MMP inhibition (doxycycline, 5.4 mg/kg/day, 24 weeks), there were no significant differences in TUNEL-positive cells detected between WKY rats and SHRs. b, c The SHR has lower capillary length density (* for capillaries in cardiac muscle in b, and green network in cremaster muscle in c). Chronic MMP inhibition increased microvascular length density in the SHR cremaster muscle. Apoptosis and cardiac capillary density measurements are derived from 4 rats/group and 8 cardiac cross-sections per heart. Cremaster muscle capillary density measurements are derived from 4 rats per group with one capillary region per cremaster muscle. * p < 0.05 SHR vs. WKY; ** p < 0.05 with vs. without doxycycline.