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Rapamycin inhibits VEGF-induced microvascular hyperpermeability in vivo. | LitMetric

Rapamycin inhibits VEGF-induced microvascular hyperpermeability in vivo.

Microcirculation

Program in Vascular Biology, Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ 07101-1709, USA.

Published: February 2010

AI Article Synopsis

Article Abstract

Objective: To test the hypothesis that rapamycin inhibits induced microvascular hyperpermeability directly in vivo.

Methods: Male golden Syrian hamsters (80-120 g) were treated with either rapamycin (at 0.1, 0.5, 2, and 10 mg/kg i.p.) or vehicle at 24 hours and at 1 hour prior to preparation of the cheek pouch. Caveolin-1 scaffolding (1 mg/kg; positive inhibitory control) was injected i.p. 24 hours prior to the experiment. 10(-8) M vascular endothelial growth factor (VEGF) or 10(-7) M platelet-activating factor (PAF) were topically applied to the cheek pouch. Microvascular permeability and arteriolar diameter were assessed using integrated optical intensity (IOI) and vascular wall imaging, respectively.

Results: Rapamycin at 0.1 and 0.5 mg/kg significantly reduced VEGF-stimulated mean IOI from 63.0 +/- 4.2 to 9.7 +/- 5.0 (85% reduction, P < 0.001) and 3.6 +/- 2.7 (95% reduction, P < 0.001), respectively. Rapamycin at 2 mg/kg also lowered VEGF-stimulated hyperpermeability (40% reduction, P < 0.05). However, 10 mg/kg rapamycin increased VEGF-induced microvascular hyperpermeability. Rapamycin at 0.5 mg/kg attenuated VEGF-induced vasodilation and PAF-induced hyperpermeability, but did not inhibit PAF-induced vasoconstriction.

Conclusions: At therapeutically relevant concentrations, rapamycin inhibits VEGF- and PAF-induced microvascular permeability. This inhibition is (i) a direct effect on the endothelial barrier, and (ii) independent of arteriolar vasodilation. Rapamycin at 10 mg/kg stimulates effectors that increase microvascular permeability.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925471PMC
http://dx.doi.org/10.1111/j.1549-8719.2009.00012.xDOI Listing

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