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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/H2394    most recent 00628.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Bratz, I. N. Articles by Kanagy, N. L. Search for Related Content PubMed PubMed Citation Articles by Bratz, I. N. Articles by Kanagy, N. L.

Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function

Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-0218

Submitted 24 June 2004 ; accepted in final form 9 August 2004

We reported previously that endothelium-intact superior mesenteric arteries (SMA) from N-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 (NO) synthase (NOS) inhibition increases cyclooxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS-induced dilation and increased COX product-induced constriction. We observed that the EC₅₀ for NE is lower in LHR SMA compared with control SMA (control –6.37 ± 0.04, LHR –7.89 ± 0.09 log mol/l; P < 0.05). Endothelium removal lowered the EC₅₀ (control –7.95 ± 0.11, LHR –8.44 ± 0.13 log mol/l; P < 0.05) and increased maximum tension in control (control 1,036 ± 38 vs. 893 ± 21 mg; P < 0.05) but not LHR (928 ± 30 vs. 1,066 ± 31 mg) SMA. 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 that COX products augment contraction. Indomethacin did not affect NE-induced contraction in L-NNA-treated or denuded arteries. In control SMA loaded with the fluorescent NO indicator 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, indomethacin increased and L-NNA decreased NO release. Therefore, COX products appear to inhibit NO production to augment NE-induced 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.

norepinephrine; acetylcholine; endothelial cells; vascular smooth muscle cells

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