Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors

Curcumin has wound healing attributes mediated through a plethora of biological activities that in general are not ascribed to specific receptors. Recently we have demonstrated that i.v. curcumin limits burn injury progression in a rat model. Since decreased microvascular perfusion is a central element of burn injury progression, we hypothesized that curcumin may induce vasodilation in peripheral arterioles, to improve perfusion. Using mucosal microcirculation as an in situ assay, cheek pouch tissue was exteriorized in anesthetized (phentobarbital 70 mg/kg i.p.) male hamsters (N=60) to observe the terminal feed arterioles (~8μm diameter) and the immediately upstream arcade arterioles (~20μm). Curcumin (10(−12) – 10(−4)mol/L) was applied dose-wise (micropipette, 60 seconds). Subnanomolar curcumin dilated whereas micromolar doses constricted the arterioles. For the terminal arteriole: vasodilation logEC50 −10.3±0.2, peak dilation +39±1%; vasconstriction logEC50 −8.0±0.4, peak constriction −14±2%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (β-Ad antagonist) enhanced constriction by removing the vasodilation response to curcumin. Phentolamine (α-Ad antagonist) enhanced dilation to curcumin by removing the vasoconstriction response. Thus, the curcumin vasomotor activity on microcirculation was α-Ad and β-Ad receptor-dependent and its net vasoactive effect was concentration and time dependent.