Indigo carmine enhances phenylephrine-induced contractions in an isolated rat aorta

다국어 초록 (Multilingual Abstract)

Background: The intravenous administration of indigo carmine has been reported to produce transiently increased blood pressure in patients. The goal of this in vitro study was to examine the effect of indigo carmine on phenylephrine-induced contractions in an isolated rat aorta and to determine the associated cellular mechanism with particular focus on the endothelium-derived vasodilators.
Methods: The concentration-response curves for phenylephrine were generated in the presence or absence of indigo carmine. Phenylephrine concentration-response curves were generated for the endothelium-intact rings pretreated independently with a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), a cyclooxygenase inhibitor, indomethacin, and a low-molecular-weight superoxide anion scavenger, tiron, in the presence or absence of indigo carmine. The fluorescence of oxidized dichlorofluorescein was measured in rat aortic vascular smooth muscle cells cultured in the control, indigo carmine alone and tiron plus indigo carmine.
Results: Indigo carmine (10^-5 M) increased the phenylephrine-induced maximum contraction in the endotheliumintact rings with or without indomethacin, whereas indigo carmine produced a slight leftward shift in the phenylephrine concentration-response curves in the endothelium-denuded rings and L-NAME-pretreated endothelium-intact rings. In the endothelium-intact rings pretreated with tiron (10^-2 M), indigo carmine did not alter phenylephrine concentration-response curves significantly. Indigo carmine (10^-5 M) increased the fluorescence of oxidized dichlorofluorescein in the vascular smooth muscle cells, whereas tiron abolished the indigo carmineinduced increase in oxidized dichlorofluorescein fluorescence.
Conclusions: Indigo carmine increases the phenylephrine-induced contraction mainly through an endotheliumdependent mechanism involving the inactivation of nitric oxide caused by the increased production of reactive oxygen species.

참고문헌 (Reference)

1 Kim HJ, "Transforming growth factor-β1 is a molecular target for the peroxisome proliferator-activated receptor delta" 102 : 193-200, 2008

2 Wu CC, "The vasopressor effect of indigo carmine" 17 : 131-137, 1969

3 Seki S, "Superoxide anion scavengers restore NO-mediated pulmonary vasodilation after lung transplantation" 276 : H42-H46, 1999

4 Busse R, "Signal transduction in endotheliumdependent vasodilation" 14 (14): 2-9, 1993

5 Jeffords DL, "Severe hypertensive reaction to indigo carmine" 9 : 180-181, 1977

6 Martin W, "Selective blockade of endothelium-dependent and gylceryl trinitrateinduced relaxation by hemoglobin and by methylene blue in the rabbit aorta" 232 : 708-716, 1985

7 Zhang Z, "Role of reactive oxygen species and MAPKs in vanadate-induced G2/M phase arrest" 34 : 1333-1342, 2003

8 Ng TY, "Reaction to indigo carmine" 116 : 132-133, 1976

9 Kohno Y, "Production of superoxide radical in reductive metabolism of a synthetic foodcoloring agents, indigocarmine, and related compounds" 77 : 601-614, 2005

10 Fortuño A, "Oxidative stress and vascular remodeling" 90 : 457-462, 2005

11 Christensen KL, "Location of resistance arteries" 38 : 1-12, 2001

12 Chang KS, "Indigo carmine inhibits endothelium- dependent and -independent vasodilation" 27 : 228-234, 1996

13 Watanabe M, "In vivo effect of methylene blue on endothelium-dependent and endotheliumindependent dilations of brain microvessels in mice" 62 : 86-90, 1988

14 Deture FA, "Evaluation of indigo carmine as an indicator of renal function" 112 : 693-696, 1974

15 Arnal JF, "Endotheliumderived nitric oxide and vascular physiology and pathology" 55 : 1078-1087, 1999

16 Hatake K, "Endothelium-dependent relaxation resistant to NG-nitro-L-arginine in rat aorta" 274 : 25-32, 1995

17 Sohn JT, "Effect of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta" Australian Society of Anaesthetists 32 (32): 476-481, 2004

18 Park SE, "Diazepam attenuates phenylephrine-induced contractions in rat aorta" LIPPINCOTT WILLIAMS & WILKINS 102 : 682-689, 2006

19 Kim HJ, "DIRECT EFFECT OF DEXMEDETOMIDINE ON RAT ISOLATED AORTA INVOLVES ENDOTHELIAL NITRIC OXIDE SYNTHESIS AND ACTIVATION OF THE LIPOXYGENASE PATHWAY" Blackwell Science Asia 36 (36): 406-412, 2009

20 Kennedy WF Jr, "Cardiovascular and respiratory effects of indigo carmine" 100 : 775-778, 1968