Vasoactive effects of nanomolar curcumin in arterioles is mediated by adrenergic receptors.

Curcumin is a highly potent antioxidant associated with ameliorating oxidative stress and inflammation. Here we report for the first time that sub‐nanomolar curcumin has potent vasomotor activity. Arteriolar response to micropipette applied curcumin was tested in the mucosal region of the cheek pouch tissue of anesthetized (70 mg/kg pentobarbital) hamsters (N=30) using intravital microscopy. Diameter was recorded for the feed of a terminal arteriolar network (baseline 8±2um) and the arcade arteriole (22±11um) that supplied it. Curcumin (10‐12 ‐ 10‐4M, 60 s) induced a biphasic response over time and with increasing doses, inconsistent with vasomotion. An initial dilation, predominant at low doses, was followed by constriction, predominant at high doses. The fitted logEC50 and peak responses were similar for the arcade and feed. Dilation, logEC50 − 9.5±0.3, peak dilation +40±8%. Constriction, logEC50 − 8.5±0.4, peak constriction − 15±5%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (beta‐adrenergic antagonist) removed dilation, enhancing constriction to curcumin. Phentolamine (alpha‐adrenergic antagonist) removed constriction, enhancing dilation to curcumin. Thus curcumin modulates arteriolar diameter via the adrenergic receptors in a dose sensitive manner. (AHA 0655908T, Armed Forces Institute of Regenerative Medicine).