title: Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats.
abstract: During ventilatory acclimatization to hypoxia (VAH), time-dependent increases in ventilation lower Pco(2) levels, and this persists on return to normoxia. We hypothesized that plasticity in the caudal nucleus tractus solitarii (NTS) contributes to VAH, as the NTS receives the first synapse from the carotid body chemoreceptor afferents and also contains CO(2)-sensitive neurons. We lesioned cells in the caudal NTS containing the neurokinin-1 receptor by microinjecting the neurotoxin saporin conjugated to substance P and measured ventilatory responses in awake, unrestrained rats 18 days later. Lesions did not affect hypoxic or hypercapnic ventilatory responses in normoxic control rats, in contrast to published reports for similar lesions in other central chemosensitive areas. Also, lesions did not affect the hypercapnic ventilatory response in chronically hypoxic rats (inspired Po(2) = 90 Torr for 7 days). These results suggest functional differences between central chemoreceptor sites. However, lesions significantly increased ventilation in normoxia or acute hypoxia in chronically hypoxic rats. Hence, chronic hypoxia increases an inhibitory effect of neurokinin-1 receptor neurons in the NTS on ventilatory drive, indicating that these neurons contribute to plasticity during chronic hypoxia, although such plasticity does not explain VAH.
authors: Division of Physiology, Department of Medicine, University of California, San Diego, USA. kawilki@emory.edu
authors: Katherine A
authors: KA
authors: Wilkinson
authors: Zhenxing
authors: Z
authors: Fu
authors: Frank L
authors: FL
authors: Powell
references: Br J Pharmacol. 2000 Mar;129(6):1121-31
references: 10725260
references: J Appl Physiol (1985). 1990 Jun;68(6):2631-9
references: 1696574
references: J Appl Physiol (1985). 2001 Apr;90(4):1247-57
references: 11247921
references: Am J Physiol. 1993 Jan;264(1 Pt 2):R41-50
references: 8381618
references: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2622-6
references: 7535928
references: Brain Res. 2006 Nov 13;1119(1):165-73
references: 16982039
references: J Appl Physiol Respir Environ Exerc Physiol. 1978 Oct;45(4):644-7
references: 101497
references: J Neurophysiol. 2009 Sep;102(3):1577-90
references: 19553484
references: Respir Physiol Neurobiol. 2007 Jul 1;157(1):154-61
references: 17291837
references: Brain Res. 2000 Feb 28;857(1-2):99-109
references: 10700557
references: J Appl Physiol (1985). 2006 Dec;101(6):1596-606
references: 16902062
references: Neurosci Lett. 1986 Aug 15;69(1):94-7
references: 2427979
references: J Appl Physiol (1985). 1997 Feb;82(2):469-79
references: 9049726
references: Neuroscience. 2007 Mar 30;145(3):1168-81
references: 17293052
references: J Appl Physiol (1985). 2004 Dec;97(6):2236-47
references: 15322066
references: Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R549-57
references: 18056985
references: J Appl Physiol (1985). 1991 Oct;71(4):1364-75
references: 1757359
references: Pflugers Arch. 2008 Mar;455(6):1119-28
references: 17851683
references: Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1449-56
references: 16778062
references: Brain Res. 2004 Apr 23;1006(1):107-13
references: 15047029
references: J Appl Physiol (1985). 2010 May;108(5):1417-24
references: 20133433
references: Respir Physiol Neurobiol. 2008 Dec 31;164(3):394-400
references: 18824146
references: J Appl Physiol (1985). 1996 Jan;80(1):108-15
references: 8847290
references: J Physiol. 1984 Feb;347:397-409
references: 6707961
references: Pain. 2001 Jul;93(1):43-50
references: 11406337
references: Gastroenterology. 2006 May;130(6):1729-42
references: 16697737
references: J Physiol. 2002 Oct 15;544(2):603-16
references: 12381830
references: J Appl Physiol (1985). 2002 May;92(5):2119-30
references: 11960965
references: J Neurosci Methods. 1980 Dec;3(2):129-49
references: 6110810
references: Neuroscience. 1990;36(1):207-16
references: 2120613
references: Respir Physiol Neurobiol. 2009 Sep 30;168(3):272-80
references: 19619674
references: J Appl Physiol (1985). 1999 Sep;87(3):910-9
references: 10484557
references: Nat Neurosci. 2001 Sep;4(9):927-30
references: 11528424
references: Br J Pharmacol. 2000 Mar;129(6):1132-9
references: 10725261
references: J Appl Physiol (1985). 1993 Apr;74(4):1635-40
references: 8514677
references: J Appl Physiol (1985). 1997 Aug;83(2):420-8
references: 9262436
references: Nat Neurosci. 2004 Dec;7(12):1360-9
references: 15558061
references: Acta Physiol Scand. 2003 Mar;177(3):377-84
references: 12609009
references: Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R763-73
references: 19144749
references: Neurosci Lett. 1997 Jul 18;230(2):97-100
references: 9259473
references: J Appl Physiol (1985). 2010 Aug;109(2):424-30
references: 20489036
references: Neuroscience. 2003;119(1):201-14
references: 12763081
references: Trends Neurosci. 2003 Dec;26(12):696-705
references: 14624855
references: Neuroscience. 1987 Jul;22(1):237-50
references: 3627444
references: J Physiol. 1988 Dec;406:99-114
references: 3254424
references: Brain Res. 1991 Apr 19;546(2):211-6
references: 1712658
references: Exp Physiol. 2006 Jan;91(1):59-72
references: 16239249
references: Exp Brain Res. 1989;76(3):656-61
references: 2507342
references: Eur J Neurosci. 2002 Sep;16(5):907-20
references: 12372027
references: J Neurosci. 2009 Mar 4;29(9):2754-61
references: 19261870
references: J Physiol. 1999 Feb 1;514 ( Pt 3):829-41
references: 9882754
references: J Physiol. 2004 Apr 1;556(Pt 1):235-53
references: 14724193
references: J Appl Physiol (1985). 1999 Aug;87(2):817-23
references: 10444644
references: Prog Brain Res. 1986;67:295-314
references: 3823479
references: J Appl Physiol (1985). 1993 Jul;75(1):5-14
references: 8376301
references: J Comp Neurol. 1994 Sep 8;347(2):249-74
references: 7814667
references: Adv Exp Med Biol. 2001;499:27-32
references: 11729890
references: Respir Physiol Neurobiol. 2010 Apr 15;171(1):46-53
references: 20117251
references: Acta Physiol Scand. 1981 Dec;113(4):541-3
references: 6182745
references: J Appl Physiol (1985). 2011 Jan;110(1):1-8
references: 21071595
references: J Physiol. 2008 Jun 15;586(12):2975-91
references: 18440993
references: Acta Physiol Scand. 1985 Jul;124(3):449-55
references: 2413713
references: J Appl Physiol (1985). 2008 Aug;105(2):404-16
references: 18535135