title: Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors.
abstract: 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 intravenous administration of curcumin limits burn injury progression in a rat model. As 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(-1) intraperitoneal) male hamsters (N=60) to observe the terminal feed arterioles (∼8 μm diameter) and the immediately upstream arcade arterioles (∼20 μm). Curcumin (10(-12)-10(-4) mol l(-1)) was applied dose-wise (micropipette, 60 seconds). Subnanomolar curcumin dilated, whereas micromolar doses constricted, the arterioles. For the terminal arteriole: vasodilation logEC(50) -10.3±0.2, peak dilation +39±1%; vasconstriction logEC(50) -8.0±0.4, peak constriction -14±2%. Simultaneous atropine (muscarinic antagonist) or PD142893 (endothelin antagonist) had no effect. Propranolol (β-adrenergic receptor (β-Ad) antagonist) enhanced constriction by removing the vasodilation response to curcumin. Phentolamine (α-adrenergic receptor (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.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794-5281, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dewar
authors.forename: Richard A
authors.initials: RA
authors.lastname: Clark
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Singer
authors.forename: Mary D
authors.initials: MD
authors.lastname: Frame
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D006224:Cricetinae; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009061:Mouth Mucosa / Q000098:blood supply / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D001285:Atropine; D011433:Propranolol; D003474:Curcumin; D010646:Phentolamine