Angiotensin II treatment significantly increased the ischemic/nonischemic leg ratio for angiographic score and capillary number by 2.6- and 2-fold, respectively, compared with controls (P<0.01).
Does Angiotensin II improve angiogenesis in ischemic hindlimb models?
Subhypertensive doses of Angiotensin II enhance ischemia-induced angiogenesis through an AT1 receptor-mediated, VEGF/eNOS-dependent pathway.
Effect estimate: 2.6-fold increase in angiographic score and 2-fold increase in capillary number
p-value: p=<0.01
We assessed the role of angiotensin (Ang) II in ischemia-induced angiogenesis and analyzed the molecular pathways involved in such an effect. Ischemia was produced by unilateral artery femoral occlusion in control, in valsartan-treated (Ang II receptor type I antagonist, 20 mg/kg per day), in Ang II-treated (5 ng/kg per min), and in Ang II and valsartan-treated rats. After 28 days, angiogenesis was assessed by microangiography and capillary density measurement in hindlimbs. The ischemic/nonischemic leg ratio for angiographic score and capillary number increased by 2.6- and 2-fold, respectively, in Ang II-treated rats compared with controls (P<0.01). This was associated with an increase in vascular endothelial growth factor (VEGF; 1.6-fold) and endothelial NO synthase (eNOS; 1.8-fold) protein content within the ischemic leg, assessed by Western blot. Angiotensin type 1 receptor blockade and administration of VEGF neutralizing antibody (2.5 microg IP, twice a week) in Ang II-treated rats completely prevented such Ang II angiogenic effects. The key role of eNOS was then emphasized by using mice deficient in gene encoding for eNOS. In wild-type mice, Ang II (0.3 mg/kg per min) treatment increased by 1.7- and 1.6-fold the ischemic/nonischemic leg for angiographic score and blood perfusion (assessed by laser Doppler perfusion imaging) ratios, respectively (P<0.01). Conversely, no significant changes were observed in Ang II-treated mice deficient in gene encoding for eNOS. Subhypertensive dose of Ang II enhanced angiogenesis associated with tissue ischemia through angiotensin type 1 receptor activation that involved the VEGF/eNOS-dependent pathway.
Tamarat et al. (Fri,) conducted a other in Ischemia-induced angiogenesis. Angiotensin II vs. Control was evaluated on Angiogenesis assessed by microangiography and capillary density measurement (2.6-fold increase in angiographic score and 2-fold increase in capillary number, p=<0.01). Angiotensin II treatment significantly increased the ischemic/nonischemic leg ratio for angiographic score and capillary number by 2.6- and 2-fold, respectively, compared with controls (P<0.01).