Rucaparib-mediated vasodilation of rat vascular tissue may be partially dependent on myosin light chain kinase.

Panel A; rucaparib (closed squares), nicotinamide (open squares) and ML-9 (open triangles) inhibit smooth muscle contraction in PE-constricted rat tail artery. Artery sections were constricted using 10 μM PE before perfusion with a solution containing 10 μM PE plus the relevant concentration of drug. Panel B; rucaparib, nicotinamide and ML-9 inhibit smooth muscle contraction in PE-constricted rat aorta. Panel C; inhibition of arterial smooth muscle contraction by rucaparib is dependent on a mechanism in addition to MLCK inhibition. Constricted vessel segments were relaxed to the maximal degree achievable with ML-9, before being challenged with a relaxing cocktail of ML-9 plus rucaparib. The histograms illustrate the additive effects that were observed in the cases of both tail artery (left) and aorta (right). ** p<0.01, *** p<0.001 versus relaxation evoked by rucaparib alone; ^ΔΔ p<0.01 versus ML-9 alone. Bars represent mean of at least three independent experiments. Arteries from at least three rats were used per test. Error bars represent SEM. Panel D; rucaparib (closed squares) inhibits MLCK activity with ten times the potency of ML-9 (open triangles). Kinase activity was analyzed using the Millipore IC₅₀Profiler Express service. Points represent results of duplicate experiments. Error bars represent SEM.