Therapeutic approaches using nitric oxide in infants and children.
Pulmonary hypertension contributes significantly to the morbidity and mortality associated with many pediatric pulmonary and cardiac diseases. Nitric oxide, a gas molecule, is a unique pharmaceutical agent that can be inhaled and thus delivered directly to the lung. Inhaled nitric oxide was approved by the FDA in 1999 as a therapy for infants with persistent pulmonary hypertension. Since then, the use of inhaled nitric oxide has expanded to other neonatal and pediatric conditions, and our knowledge of its properties and mechanisms of action has increased tremendously. This review discusses the physiology of nitric oxide signaling, the most common indications for its clinical use, and promising new investigations that may enhance endogenous production of nitric oxide and/or improve vascular response to it.
Department of Pediatrics, Children's Memorial Hospital and Northwestern University's Feinberg School of Medicine, Chicago, IL 60614, USA. r-steinhorn@northwestern.edu
Robin H
RH
Steinhorn
D000280:Administration, Inhalation; D020013:Calcium Signaling / Q000187:drug effects; D002648:Child; D017277:Drug Approval; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007223:Infant; D058990:Molecular Targeted Therapy / Q000639:trends; D009569:Nitric Oxide / Q000502:physiology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D014481:United States; D014486:United States Food and Drug Administration; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide
Pediatr Res. 2004 Mar;55(3):413-8
14711900
N Engl J Med. 1997 Feb 27;336(9):597-604
9036320
Biol Neonate. 2006;90(2):135-44
16582538
Annu Rev Physiol. 2002;64:749-74
11826287
Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L46-56
18024721
N Engl J Med. 1993 Feb 11;328(6):399-405
8357359
Circulation. 1995 Aug 1;92(3):606-13
7634475
Pediatr Res. 2009 Nov;66(5):539-44
19680165
Respir Physiol Neurobiol. 2010 Dec 31;174(3):272-81
20804862
N Engl J Med. 2003 Nov 27;349(22):2099-107
14645637
N Engl J Med. 2001 Jun 14;344(24):1832-8
11407344
Am J Physiol Lung Cell Mol Physiol. 2008 Dec;295(6):L976-8
18931050
Pediatr Res. 1998 Feb;43(2):163-8
9475279
J Clin Invest. 1994 Jun;93(6):2675-83
8201005
N Engl J Med. 2005 Jul 7;353(1):13-22
16000352
Cochrane Database Syst Rev. 2003;(1):CD002787
12535438
Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L450-9
15591412
Biochem Pharmacol. 2002 May 1;63(9):1763-72
12007579
Clin Perinatol. 1984 Oct;11(3):525-49
6386268
Am J Physiol Lung Cell Mol Physiol. 2008 Nov;295(5):L881-8
18757525
J Pediatr. 2007 Mar;150(3):235-40, 240.e1
17307536
Am J Physiol. 1990 Dec;259(6 Pt 2):H1921-7
2260716
Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L150-9
20453164
Anesthesiology. 2000 Jun;92(6):1702-12
10839922
N Engl J Med. 1997 Feb 27;336(9):605-10
9032045
Am J Physiol. 1997 Mar;272(3 Pt 1):L400-6
9124595
Pediatrics. 2000 Jan;105(1 Pt 1):14-20
10617698
Am J Physiol. 1997 May;272(5 Pt 1):L1005-12
9176267
Circ Res. 2008 Feb 1;102(2):226-33
17991881
Crit Care Med. 2001 May;29(5):1000-5
11378612
Circ Res. 2003 Apr 4;92(6):683-91
12609968
J Thorac Cardiovasc Surg. 2006 Jul;132(1):58-65
16798303
Pediatr Crit Care Med. 2010 Mar;11(2 Suppl):S30-6
20216160
Clin Perinatol. 2004 Sep;31(3):591-611
15325540
J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26
17662768
Pediatrics. 1998 Mar;101(3 Pt 1):325-34
9480993
Am J Respir Crit Care Med. 2006 Dec 15;174(12):1370-7
17008638
Pediatr Res. 1998 Sep;44(3):338-43
9727710
Circulation. 2003 Mar 4;107(8):1195-201
12615801
Acta Pharmacol Sin. 2010 Feb;31(2):175-83
20139900
Am J Respir Crit Care Med. 2002 Apr 15;165(8):1098-102
11956051
Pediatrics. 2006 Apr;117(4):1077-83
16585301
Am J Physiol Lung Cell Mol Physiol. 2004 Jun;286(6):L1244-54
14766668
Curr Opin Cell Biol. 2000 Apr;12(2):174-9
10712916
N Engl J Med. 2006 Jul 27;355(4):343-53
16870913
Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L232-41
16143585
Am J Respir Crit Care Med. 2007 Feb 1;175(3):256-62
17082495
Am J Physiol Lung Cell Mol Physiol. 2010 Jul;299(1):L109-16
20400523
Pediatr Res. 2006 Jan;59(1):137-41
16326983
Pediatrics. 2004 Mar;113(3 Pt 1):559-64
14993550
Am J Physiol. 1994 Jun;266(6 Pt 1):L635-41
7517640
Circulation. 2005 Apr 26;111(16):2126-33
15824200
Am J Physiol Lung Cell Mol Physiol. 2008 Dec;295(6):L979-87
18790993
Circulation. 2002 Sep 24;106(12 Suppl 1):I76-81
12354713
Am J Physiol Lung Cell Mol Physiol. 2005 Oct;289(4):L660-6
15937064
Pediatr Clin North Am. 2009 Jun;56(3):579-600, Table of Contents
19501693
Mol Interv. 2003 Aug;3(5):253-63
14993439
Am J Physiol. 1995 Apr;268(4 Pt 2):H1483-9
7733349
Lancet. 2010 Jul 31;376(9738):346-54
20655106
Am J Physiol. 1998 Nov;275(5):L931-41
9815111
N Engl J Med. 2000 Feb 17;342(7):469-74
10675427
Am J Physiol Lung Cell Mol Physiol. 2010 Aug;299(2):L147-9
20525916
Am J Physiol Lung Cell Mol Physiol. 2001 May;280(5):L923-9
11290516
Pediatr Crit Care Med. 2010 Mar;11(2 Suppl):S79-84
20216169
Am J Physiol Lung Cell Mol Physiol. 2001 Oct;281(4):L1011-20
11557605
Am J Respir Crit Care Med. 2001 Sep 1;164(5):834-9
11549542
BMC Pediatr. 2010 Mar 23;10:15
20331899
J Perinatol. 2008 Dec;28 Suppl 3:S67-71
19057613
Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L749-58
12676765
J Pediatr. 2008 Oct;153(4):525-9
18534620
Antioxid Redox Signal. 2011 Sep 15;15(6):1497-506
20919937
Am J Physiol Heart Circ Physiol. 2001 Jan;280(1):H311-7
11123246
J Clin Invest. 2003 Apr;111(8):1201-9
12697739
Pediatr Res. 2006 Jun;59(6):767-72
16641207
Pediatr Pulmonol. 2001 Feb;31(2):97-105
11180684
Am J Respir Crit Care Med. 1998 Jul;158(1):279-88
9655741
Pediatr Res. 2007 Sep;62(3):313-8
17622960
Am J Physiol. 1993 Jul;265(1 Pt 2):H376-80
8342654
Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L202-8
10645908
J Pharmacol Exp Ther. 1997 Nov;283(2):619-24
9353377
Pediatr Crit Care Med. 2004 Nov;5(6):517-20
15530186
Am J Physiol Lung Cell Mol Physiol. 2002 Dec;283(6):L1192-9
12388364
Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):1877-85
17541026
Lancet. 2000 Oct 28;356(9240):1464-9
11081528
J Pediatr. 1999 Apr;134(4):406-12
10190913
N Engl J Med. 2006 Jul 27;355(4):354-64
16870914
Am J Physiol Lung Cell Mol Physiol. 2009 Sep;297(3):L506-11
19617312