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8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo

^a Laboratory of Experimental and Clinical Interventional Cardiology, University Federico II, Naples, Italy
^* Department of Molecular and Clinical Endocrinology and Oncology, University Federico II, Naples, Italy

View larger version (33K): [in a new window]   Figure 1 (a) Effects of 8-Cl-cAMP (1, 5, and 10 µmol/liter) on the growth inhibition of rat VSMCs. Both 5 and 10 µmol/liter 8-Cl-cAMP induced a significant inhibition of VSMC proliferation at any time. (b) Western blot analysis in VSMCs untreated (control) or treated with 8-Cl-cAMP (1, 5, and 10 µmol/liter). The 8-Cl-cAMP induced a significant reduction of RI level, enhanced level of RIIß, and showed no effect on catalytic subunit (c).

View larger version (27K): [in a new window]   Figure 2 Bar graphs of neointima/media ratio (top panel) and neointimal cross-sectional area (bottom panel) of common carotid arteries from rats included in the study. The 8-Cl-cAMP and dosages administered in Protocols II, III, and IV significantly reduced both neointimal cross-sectional area and neointima/media ratio. *p < 0.05 vs. Controls and Protocol I; #p < 0.05 vs. Controls and 8-Cl-cAMP Protocol I; p < 0.05 vs. 8-Cl-cAMP Protocol III.

View larger version (91K): [in a new window]   Figure 3 Representative histologic sections stained with hematoxylin-eosin of common carotid arteries, removed 14 days after angioplasty, from (a) a normal rat (no balloon injury); (b) a control rat subjected to only balloon injury; (c) rats included in Protocol I; (d) rats included in Protocol II; (e) rats included in Protocol III; (f) rats included in Protocol IV. The 8-Cl-cAMP reduced significantly the neointima formation after balloon injury (c, d, e).

View larger version (16K): [in a new window]   Figure 4 Effects of 8-Cl-cAMP on systolic blood pressure (SBP) and heart rate (HR) in rats treated with 8-Cl-cAMP (Protocol IV). Administration of 8-Cl-cAMP did not induce significant changes in heart rate and blood pressure.