Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice.
High tidal volume ventilation is detrimental to alveolar fluid clearance (AFC), but effects of ventilation pressure (P) on AFC are unknown. In anesthetized BALB/c mice ventilated at constant tidal volume (8 ml/kg), mean AFC rate was 12.8% at 6 cmH(2)O P, but increased to 37.3% at 18 cmH(2)O P. AFC rate declined at 22 cmH(2)O P, which also induced lung damage. Increased AFC at 18 cmH(2)O P did not result from elevated plasma catecholamines, hypercapnia, or hypocapnia, but was due to augmented Na(+) and Cl(-) absorption. PKA agonists and beta-agonists stimulated AFC at 10 cmH(2)O P by upregulating amiloride-sensitive Na(+) transport. However, at 18 cmH(2)O P, PKA agonists and beta-agonists reduced AFC. At 15 cmH(2)O P, the AFC rate was intermediate (mean 26.6%), and forskolin and beta-agonists had no effect. Comparable P dependency of AFC and beta-agonist responsiveness was found in C57BL/6 mice. The effect on AFC of increasing P to 18 cmH(2)O was blocked by adenosine deaminase or an A(2b)-adenosine receptor antagonist, and could be mimicked by adenosine in mice ventilated at 10 cmH(2)O P. Modulation of adenosine signaling also resulted in altered responsiveness to beta-agonists. These findings indicate that, in the normal mouse lung, basal AFC rates and responses to beta-agonists are impacted by ventilation pressure in an adenosine-dependent manner.
Yu
Erin N Z
EN
Dept. of Veterinary Biosciences, The Ohio State Univ., 1925 Coffey Road, Columbus, OH 43210, USA.
Traylor
Zachary P
ZP
Davis
Ian C
IC
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005576:Colforsin / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009079:Mucociliary Clearance; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012121:Respiration, Artificial; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D005576:Colforsin; D000584:Amiloride; D010100:Oxygen
Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1233-7
18424620
Am J Respir Cell Mol Biol. 2004 May;30(5):720-8
14607816
J Physiol. 2007 Jul 15;582(Pt 2):777-88
17430990
Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L722-31
11504701
Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L281-9
17435077
Am J Respir Crit Care Med. 2006 Feb 1;173(3):334-44
16254273
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4083-8
17360481
Am J Respir Crit Care Med. 2006 Mar 15;173(6):673-82
16387801
Am J Respir Crit Care Med. 2007 Sep 15;176(6):582-90
17556717
Intensive Care Med. 2007 Jul;33(7):1229-1240
17525842
Am J Respir Cell Mol Biol. 2009 Sep;41(3):261-70
19131639
Am J Respir Crit Care Med. 2008 Nov 1;178(9):969-76
18689466
Respir Physiol Neurobiol. 2004 Jun 25;140(3):283-91
15186789
J Appl Physiol (1985). 2000 Aug;89(2):672-9
10926653
Circ Res. 2004 Apr 30;94(8):1091-100
15016730
N Engl J Med. 2000 May 4;342(18):1301-8
10793162
Am J Respir Crit Care Med. 2001 May;163(6):1376-83
11371404
Anesthesiology. 1998 Mar;88(3):751-60
9523820
Acta Physiol Scand. 2002 Apr;174(4):367-75
11942924
Am J Physiol. 1998 Dec;275(6):L1127-33
9843850
Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1099-109
15681398
Am J Respir Crit Care Med. 2005 Jun 1;171(11):1267-71
15764729
Chest. 2007 Mar;131(3):913-920
17356114
Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L791-8
12562562
J Gen Physiol. 2002 Feb;119(2):199-207
11815669
Am J Respir Cell Mol Biol. 2008 Jan;38(1):32-7
17690328
Anesthesiology. 2007 May;106(5):944-51
17457125
Crit Care Med. 2003 Apr;31(4 Suppl):S248-52
12682448
J Clin Invest. 2008 Feb;118(2):752-62
18188452
Am J Respir Crit Care Med. 2002 Jan 15;165(2):242-9
11790662
J Immunol. 2007 Jun 15;178(12):8127-37
17548651
Chest. 2007 Mar;131(3):921-929
17356115
Nat Med. 2007 Apr;13(4):406-8
17415371
Am J Respir Cell Mol Biol. 2006 Jun;34(6):670-6
16439801
Respir Res. 2003;4:4
12783622
J Clin Invest. 2008 Oct;118(10):3301-15
18787641
Am J Respir Crit Care Med. 2006 Feb 1;173(3):281-7
16254268
Am J Physiol. 1995 Jun;268(6 Pt 1):L1036-46
7611426
Adv Exp Med Biol. 2007;618:127-40
18269193
Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L112-20
12948936
Chest. 2008 Apr;133(4):845-52
17989152
Am J Respir Crit Care Med. 1999 Feb;159(2):626-33
9927383
Am J Physiol. 1999 Jul;277(1):L167-73
10409244
Am J Respir Cell Mol Biol. 2008 Feb;38(2):127-34
17709598