The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function

被引:49
作者
Casadei, Barbara [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England
关键词
D O I
10.1113/expphysiol.2006.035493
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The recent discovery of a NOS1 gene product (i.e. a neuronal-like isoform of nitric oxide synthase or nNOS) in the mammalian left ventricular (LV) myocardium has provided a new key for the interpretation of the complex experimental evidence supporting a role for myocardial constitutive nitric oxide (NO) production in the regulation of basal and beta-badrenergic cardiac function. Importantly, nNOS gene deletion has been associated with more severe LV remodelling and functional deterioration in murine models of myocardial infarction, suggesting that nNOS-derived NO may also be involved in the myocardial response to injury. To date, the mechanisms by which nNOS influences myocardial pathophysiology remain incompletely understood. In particular, it seems over simplistic to assume that all aspects of the myocardial phenotype of nNOS knockout (nNOS(-/-)) mice are a direct consequence of lack of NO production from this source. Emerging data showing co-localisation of xanthine oxidoreductase (XOR) and nNOS in the sarcoplasmic reticulum of rodents, and increased XOR activity in the nNOS(-/-) myocardium, suggest that nNOS gene deletion may have wider implications on the myocardial redox state. Similarly, the mechanisms regulating the targeting of myocardial nNOS to different subcellular compartments and the functional consequences of intracellular nNOS trafficking have not been fully established. Whether this information could be translated into a better understanding and management of human heart failure remains the most important challenge for future investigations.
引用
收藏
页码:943 / 955
页数:13
相关论文
共 83 条
  • [71] Nitric oxide activates skeletal and cardiac ryanodine receptors
    Stoyanovsky, D
    Murphy, T
    Anno, PR
    Kim, YM
    Salama, G
    [J]. CELL CALCIUM, 1997, 21 (01) : 19 - 29
  • [72] Chronic treatment with allopurinol boosts survival and cardiac contractility in murine postischemic cardiomyopathy
    Stull, LB
    Leppo, MK
    Szweda, L
    Gao, WD
    Marbán, E
    [J]. CIRCULATION RESEARCH, 2004, 95 (10) : 1005 - 1011
  • [73] Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel α1 subunit and reduced ischemia/reperfusion injury
    Sun, JH
    Picht, E
    Ginsburg, KS
    Bers, DM
    Steenbergen, C
    Murphy, E
    [J]. CIRCULATION RESEARCH, 2006, 98 (03) : 403 - 411
  • [74] Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load
    Takimoto, E
    Champion, HC
    Li, MX
    Ren, SX
    Rodriguez, ER
    Tavazzi, B
    Lazzarino, G
    Paolocci, N
    Gabrielson, KL
    Wang, YB
    Kass, DA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (05) : 1221 - 1231
  • [75] TRAFFORD AW, 2001, FRONT BIOSCI, V6, P53
  • [76] Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase
    Vandecasteele, G
    Eschenhagen, T
    Scholz, H
    Stein, B
    Verde, I
    Fischmeister, R
    [J]. NATURE MEDICINE, 1999, 5 (03) : 331 - 334
  • [77] Effects of nNOS antisense in the paraventricular nucleus on blood pressure and heart rate in rats with heart failure
    Wang, Y
    Liu, XF
    Cornish, KG
    Zucker, IH
    Patel, KP
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 288 (01): : H205 - H213
  • [78] Wang Y, 1995, Adv Pharmacol, V34, P71
  • [79] nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure
    Wang, Y
    Patel, KP
    Cornish, KG
    Channon, KM
    Zucker, IH
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2003, 285 (04): : H1660 - H1667
  • [80] Nitric oxide synthase in cardiac sarcoplasmic reticulum
    Xu, KY
    Huso, DL
    Dawson, TM
    Bredt, DS
    Becker, LC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) : 657 - 662