Pentose phosphate pathway coordinates multiple redox-controlled relaxing mechanisms in bovine coronary arteries

被引:66
作者
Gupte, SA [1 ]
Arshad, M [1 ]
Viola, S [1 ]
Kaminski, PM [1 ]
Ungvari, Z [1 ]
Rabbani, G [1 ]
Koller, A [1 ]
Wolin, MS [1 ]
机构
[1] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2003年 / 285卷 / 06期
关键词
calcium; redox signaling; vasodilator mechanisms;
D O I
10.1152/ajpheart.00229.2003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Pentose phosphate pathway (PPP) inhibitors, 6-aminonicotinamide (6-AN) and epiandrosterone (Epi), were employed to examine whether changes in NADP(H) redox regulates contractile force in endothelium-removed bovine coronary arteries (BCAs). 6-AN (0.01-5 mM) or Epi (1-500 muM) elicited dose-dependent relaxation in BCAs contracted with 30 mM KCl, 0.1 muM U-44619, and endothelin-1 but not with phorbol 12,13-dibutyrate, a protein kinase C activator that causes Ca2+-independent contraction. Relaxation to PPP inhibition was associated with oxidation of NADPH and glutathione (GSH). Relaxation to 6-AN was not mediated by H2O2, because it was not altered by hypoxia or the peroxide scavenger ebselen (100 muM). The thiol reductant DTT (3 mM) attenuated the relaxation to 6-AN and Epi by 30-40%. Inhibition of glycolysis or mitochondrial electron transport did not elicit relaxation in BCAs contracted with 30 mM KCl, suggesting these pathways may not be involved in relaxation elicited by PPP inhibition. High doses of K+ channel blockers [e.g., TEA (10 mM) and 4-aminopyridine (10 mM)] only partially inhibited the relaxation to 6-AN. On the basis of changes in the fura-2 fluorescence ratio, 6-AN and Epi appeared to markedly reduce intracellular Ca2+. Thus PPP inhibition oxidizes NADPH and GSH and appears to activate a novel coordination of redox-controlled relaxing mechanisms in BCAs mediated primarily through decreasing intracellular Ca2+.
引用
收藏
页码:H2316 / H2326
页数:11
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