Redox variants of NO (NO• and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms

被引:48
作者
Favaloro, Joanne L. [1 ]
Kemp-Harper, Barbara K. [2 ]
机构
[1] RMIT Univ, Sch Med Sci, Discipline Pharmaceut Sci, Bundoora W, Vic 3083, Australia
[2] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2009年 / 296卷 / 05期
基金
奥地利科学基金会; 英国医学研究理事会;
关键词
nitroxyl; hyperpolarization; soluble guanylate cyclase; K+ channels; nitric oxide; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE; SOLUBLE GUANYLYL CYCLASE; GATED K+ CHANNELS; NITROXYL ANION; POTASSIUM CHANNELS; MESENTERIC-ARTERY; PULMONARY-ARTERY; NITROGEN-OXIDE; ANGELIS SALT;
D O I
10.1152/ajpheart.00008.2009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Favaloro JL, Kemp-Harper BK. Redox variants of NO (NO center dot and HNO) elicit vasorelaxation of resistance arteries via distinct mechanisms. Am J Physiol Heart Circ Physiol 296: H1274-H1280, 2009; doi:10.1152/ajpheart.00008.2009.-The free radical form of nitric oxide (NO center dot) is a well-known mediator of vascular tone. What is not so well recognized is that NO center dot exists in several different redox forms. There is considerable evidence that NO center dot and its one-electron reduction product, nitroxyl (HNO), have pharmacologically distinct actions that extend into the regulation of the vasculature. The aim of this study was to compare the vasorelaxation mechanisms of HNO and NO center dot, including an examination of the ability of these redox variants to hyperpolarize and repolarize vascular smooth muscle cells from rat mesenteric arteries. The HNO donor Angeli's salt (0.1 nM-10 mu M) caused a concentration-dependent hyperpolarization of vessels at resting tone and a simultaneous, concentration-dependent vasorelaxation and repolarization of vessels precontracted and depolarized with methoxamine. Both vasorelaxation and repolarization responses to Angeli's salt were significantly attenuated by both the HNO scavenger L-cysteine (3 mM) and the voltage-dependent K+ (K-v) channel inhibitor 4-aminopyridine (4-AP; 1 mM) and virtually abolished by the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ; 10 mu M) or 30 mM K+. In contrast, NO center dot (0.01-1 mu M) repolarized arteries to a lesser extent than HNO, and these responses were resistant to inhibition by ODQ (10 mu M) and 4-AP (1 mM). Blockade of Kv channels (1 mM 4-AP) also significantly inhibited the repolarization response to YC-1 (0.1-10 mu M), confirming a role for sGC/cGMP in the activation of Kv channels in this preparation. We conclude that HNO causes vasorelaxation via a cGMP-dependent activation of Kv channels and that there are different profiles of vasorelaxant activity for the redox siblings HNO and NO center dot.
引用
收藏
页码:H1274 / H1280
页数:7
相关论文
共 49 条
[1]   Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase - Implications for mechanism [J].
Adak, S ;
Wang, Q ;
Stuehr, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (43) :33554-33561
[2]  
ANDREWS KL, BRIT J PHAR IN PRESS
[3]   NO+, NO(CENTER-DOT), AND NO- DONATION BY S-NITROSOTHIOLS - IMPLICATIONS FOR REGULATION OF PHYSIOLOGICAL FUNCTIONS BY S-NITROSYLATION AND ACCELERATION OF DISULFIDE FORMATION [J].
ARNELLE, DR ;
STAMLER, JS .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 318 (02) :279-285
[4]   The reduction potential of nitric oxide (NO) and its importance to NO biochemistry [J].
Bartberger, MD ;
Liu, W ;
Ford, E ;
Miranda, KM ;
Switzer, C ;
Fukuto, JM ;
Farmer, PJ ;
Wink, DA ;
Houk, KN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (17) :10958-10963
[5]   Nitroxyl increases force development in rat cardiac muscle [J].
Dai, Tieying ;
Tian, Ye ;
Tocchetti, Carlo Gabriele ;
Katori, Tatsuo ;
Murphy, Anne M. ;
Kass, David A. ;
Paolocci, Nazareno ;
Gao, Wei Dong .
JOURNAL OF PHYSIOLOGY-LONDON, 2007, 580 (03) :951-960
[6]   Nitric oxide (NO center dot), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase [J].
Dierks, EA ;
Burstyn, JN .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (12) :1593-1600
[7]   Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine [J].
Donzelli, Sonia ;
Espey, Michael Graham ;
Flores-Santana, Wilmarie ;
Switzer, Christopher H. ;
Yeh, Grace C. ;
Huang, Jinming ;
Stuehr, Dennis J. ;
King, S. Bruce ;
Miranda, Katrina M. ;
Wink, David A. .
FREE RADICAL BIOLOGY AND MEDICINE, 2008, 45 (05) :578-584
[8]   The activation of metabolites of nitric oxide synthase by metals is both redox and oxygen dependent: A new feature of nitrogen oxide signaling [J].
Donzelli, Sonia ;
Switzer, Christopher H. ;
Thomas, Douglas D. ;
Ridnour, Lisa A. ;
Espey, Michael Graham ;
Isenberg, Jeffrey S. ;
Tocchetti, Carlo G. ;
King, S. Bruce ;
Lazzarino, Giuseppe ;
Miranda, Katrina M. ;
Roberts, David D. ;
Feelisch, Martin ;
Wink, David A. .
ANTIOXIDANTS & REDOX SIGNALING, 2006, 8 (7-8) :1363-1371
[9]   Differential actions of L-cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta [J].
Ellis, A ;
Li, CG ;
Rand, MJ .
BRITISH JOURNAL OF PHARMACOLOGY, 2000, 129 (02) :315-322
[10]   The nitroxyl anion (HNO) is a potent dilator of rat coronary vasculature [J].
Favaloro, Joanne L. ;
Kemp-Harper, Barbara K. .
CARDIOVASCULAR RESEARCH, 2007, 73 (03) :587-596