| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
* To whom correspondence should be addressed. E-mail: njernigan{at}salud.unm.edu.
Chronic hypoxia (CH) increases pulmonary arterial endothelial nitric oxide (NO) synthase expression and augments endothelium-derived nitric oxide (EDNO)-dependent
pulmonary vasodilation, whereas vasodilatory responses to exogenous NO are attenuated in lungs from CH rats. We hypothesized that reactive oxygen species (ROS) inhibit NO-dependent pulmonary vasodilation following CH. To test this hypothesis, we examined responses to the EDNO-dependent vasodilator endothelin-1 (ET-1) and the NO donor, S-nitroso-N-acetyl penicillamine (SNAP) in isolated lungs from control and CH (0.5 atm, 4 wks) rats in the presence or absence of the ROS scavengers, tiron or superoxide dismutase (SOD) + catalase under normoxic or hypoxic ventilation. Isolated lungs used for SNAP experiments were
pretreated with the NOS inhibitor, N
-nitro-L-arginine (L-NNA) to eliminate influences of
endogenously produced NO. Additionally, dichlorofluorescein (DCF) fluorescence was measured as an index of ROS levels in isolated pressurized small pulmonary arteries from each
group. We found that acute hypoxia increased DCF fluorescence and attenuated vasodilatory responses to ET-1 in lungs from control rats with an intact NOS system. Furthermore, ROS scavengers augmented ET-1-induced vasodilation in lungs from both groups during hypoxic
ventilation. In contrast, upon NOS inhibition, DCF fluorescence was elevated and SNAPinduced vasodilation was diminished in arteries from CH rats vs. controls during normoxia, whereas acute hypoxia decreased DCF fluorescence which correlated with augmented reactivity to SNAP in both groups. Moreover, ROS scavengers enhanced SNAP-induced vasodilation in normoxic- ventilated lungs from CH rats similar to effects of hypoxic ventilation. We conclude
that inhibition of NOS during normoxia leads to greater ROS generation in lungs from both control and CH rats. Furthermore, NOS inhibition reveals an effect of acute hypoxia to diminish ROS levels and augment NO-mediated pulmonary vasodilation.
This article has been cited by other articles:
|
|
 |
|
  N. L. Jernigan, B. R. Walker, and T. C. Resta Reactive oxygen species mediate RhoA/Rho kinase-induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L515 - L529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Y. Song, C. F. Zwemer, S. E. Whitesall, and L. G. D'Alecy Acute and conditioned hypoxic tolerance augmented by endothelial nitric oxide synthase inhibition in mice J Appl Physiol, February 1, 2007; 102(2): 610 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sturrock, B. Cahill, K. Norman, T. P. Huecksteadt, K. Hill, K. Sanders, S. V. Karwande, J. C. Stringham, D. A. Bull, M. Gleich, et al. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L661 - L673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kopkan, A. Castillo, L. G. Navar, and D. S. A. Majid Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats Am J Physiol Renal Physiol, January 1, 2006; 290(1): F80 - F86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Leffler, L. Balabanova, A. L. Fedinec, and H. Parfenova Nitric oxide increases carbon monoxide production by piglet cerebral microvessels Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1442 - H1447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Muzaffar, N Shukla, G D Angelini, and J Y Jeremy Acute hypoxia simultaneously induces the expression of gp91phox and endothelial nitric oxide synthase in the porcine pulmonary artery Thorax, April 1, 2005; 60(4): 305 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jernigan, B. R. Walker, and T. C. Resta Endothelium-derived reactive oxygen species and endothelin-1 attenuate NO-dependent pulmonary vasodilation following chronic hypoxia Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L801 - L808. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
