title: Ascorbic acid does not improve endothelium-dependent flow-mediated dilatation of the brachial artery in patients with Raynaud's phenomenon secondary to systemic sclerosis.
abstract: Previous studies have shown that patients with Raynaud's phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud's phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud's phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud's phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 +/- 2.2% to 2.2 +/- 2.5%, ns) or placebo administration (1.2 +/- 1.9% to 1.7 +/- 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 +/- 7.4% vs 17 +/- 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud's phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.
authors.affiliation: Department of Clinical Therapeutic, Alexandra University Hospital, Athens, Greece.
authors.forename: Myron E
authors.initials: ME
authors.lastname: Mavrikakis
authors.forename: John P
authors.initials: JP
authors.lastname: Lekakis
authors.forename: Christos M
authors.initials: CM
authors.lastname: Papamichael
authors.forename: Kimon S
authors.initials: KS
authors.lastname: Stamatelopoulos
authors.forename: Ch C
authors.initials: ChC
authors.lastname: Kostopoulos
authors.forename: Stamatios F
authors.initials: SF
authors.lastname: Stamatelopoulos
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011928:Raynaud Disease / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000150:complications*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid