AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Heart Circ Physiol (August 19, 2004). doi:10.1152/ajpheart.00628.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/6/H2394    most recent
00628.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bratz, I. N
Right arrow Articles by Kanagy, N. L
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bratz, I. N
Right arrow Articles by Kanagy, N. L
Submitted on June 24, 2004
Accepted on August 9, 2004

Nitric Oxide Synthase Inhibition Hypertension Is Associated With Altered Endothelial Cyclo-Oxygenase Function

Ian N Bratz1 and Nancy L Kanagy2*

1 Department of Physiology, Louisiana State University, New Orleans, LA, USA
2 Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM, USA

* To whom correspondence should be addressed. E-mail: nkanagy{at}salud.unm.edu.

We reported previously that endothelium-intact superior mesenteric arteries (SMA) from N-{omega}-nitro-L-arginine (L-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from Control rats. Others have shown that nitric oxide synthase (NOS)-inhibition increases cyclo-oxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS dilation and increased COX product constriction. We observed that the EC50 for NE is lower in LHR SMA compared to Control (Control: -6.37 ± .04, LHR: *-7.89 ± .09 log mol/L). Endothelium removal lowered the EC50 (Control: -7.95 ± .11, LHR: *-8.44 ± .13 log mol/L) and increased maximum tension in Control (Control: *1036 ± 38 vs. 893 ± 21 mg) but not LHR SMA (928 ± 30 vs. 1066 ± 31 mg). Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (L-NNA, 10-4 mol/L) increased maximum tension and EC50 in Control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in Control arteries suggesting COX products augment contraction. Indomethacin did not affect NE contraction in L-NNA-treated or denuded arteries. In Control SMA loaded with the fluorescent NO indicator, DAF-2DA, indomethacin increased and L-NNA decreased NO release. Therefore COX products appear to inhibit NO production to augment NE contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction. * significantly different from Control for p < 0.05.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.