scholarly journals Chronic hypoxia enhances 15-lipoxygenase-mediated vasorelaxation in rabbit arteries

2009 ◽  
Vol 296 (3) ◽  
pp. H678-H688 ◽  
Author(s):  
Nitin T. Aggarwal ◽  
Sandra L. Pfister ◽  
Kathryn M. Gauthier ◽  
Yuttana Chawengsub ◽  
John E. Baker ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Chronic Hypoxia ◽  
Nordihydroguaiaretic Acid ◽  
Mesenteric Arteries ◽  
Epoxyeicosatrienoic Acids ◽  
Aortic Endothelial Cells ◽  
Rabbit Mesenteric Arteries

15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to 11,12,15-trihydroxyeicosatrienoic acids (THETAs) and 15-hydroxy-11,12-epoxyeicosatrienoic acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1 expression enhances arterial relaxations to agonists. We tested the effect of hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in rabbit arteries. The incubation of rabbit aortic endothelial cells and isolated aortas in 0.7% O2 increased 15-LO-1 expression. Rabbits were housed in a hypoxic atmosphere of 12% O2 for 5 days. 15-LO-1 expression increased in the endothelium of the arteries of rabbits in 12% O2 compared with room air. THETA and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA hyperpolarized the smooth muscle cells in indomethacin- and phenylephrine-treated mesenteric arteries of hypoxic rabbits from −29.4 ± 1 to −50.1 ± 3 mV. The hyperpolarization to AA was less in arteries of normoxic rabbits (from −26.0 ± 2 to −37 ± 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO inhibitor BW-755C. Nitric oxide and prostaglandin-independent maximum relaxations to acetylcholine (79.7 ± 2%) and AA (38.3 ± 4%) were enhanced in mesenteric arteries from hypoxic rabbits compared with the normoxic rabbits (49.7 ± 6% and 19.9 ± 2%, respectively). These relaxations were inhibited by BW-755C and nordihydroguaiaretic acid. Therefore, hypoxia increased the relaxations to agonists in the rabbit mesenteric arteries by enhancing endothelial 15-LO-1 expression and synthesis of the hyperpolarizing factors THETA and HEETA.

Immunohistochemical demonstration of a paracrine role of nitric oxide in bronchial function

1994 ◽  
Vol 267 (6) ◽  
pp. L704-L711 ◽  
Author(s):  
A. Rengasamy ◽  
C. Xue ◽  
R. A. Johns
Keyword(s):  
Nitric Oxide ◽  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Raw 264.7 Macrophages ◽  
Aortic Endothelial Cells ◽  
Arterial Endothelial Cells

We addressed the controversial role of nitric oxide (NO) in bronchial function by an immunohistochemical study of the localization of NO synthase (NOS) and its effector protein, soluble guanylate cyclase, in rat bronchus. For this study, a monoclonal antibody to the bovine constitutive neuronal NOS was developed and characterized. In Western blot analysis, this monoclonal antibody (anti-NOS antibody) reacted with bovine cerebellum NOS (150 kDa) as well as with structurally different NOSs from cultured bovine aortic endothelial cells (130 kDa) and cultured RAW 264.7 macrophages (130 kDa). The reactivity of anti-NOS antibody was confirmed by immunohistochemical staining of rat cerebellum, arterial endothelial cells, and cultured stimulated macrophages. When the distribution of NOS in rat airway was characterized, the anti-NOS antibody showed immunoreactivity within respiratory epithelium but not in the bronchial smooth muscle. The NADPH-diaphorase staining correlated with the immunostaining. In contrast, a monoclonal antibody to the rat lung-soluble guanylate cyclase immunostained respiratory smooth muscle but not epithelium. This study suggests a paracrine role for NO in bronchial function analogous to the function of the NOS-soluble guanylate cyclase pathway in blood vessels.

Bile acid interaction with muscarinic receptors on aortic endothelial cells results in nitric oxide-mediated smooth muscle relaxiation

2001 ◽  
Vol 120 (5) ◽  
pp. A376
Author(s):  
Sandeep Khurana ◽  
Kunrong Cheng ◽  
Richard P. Wyeth ◽  
Richard Kennedy ◽  
Jean-Pierre Raufman
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Bile Acid ◽  
Muscarinic Receptors ◽  
Acid Interaction ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

Effects of Dipyrone on Prostaglandin Production by Human Platelets and Cultured Bovine Aortic Endothelial Cells

1983 ◽  
Vol 49 (02) ◽  
pp. 132-137 ◽  
Author(s):  
A Eldor ◽  
G Polliack ◽  
I Vlodavsky ◽  
M Levy
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Ionophore A23187 ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Aortic Endothelial

SummaryDipyrone and its metabolites 4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoan- tipyrine inhibited the formation of thromboxane A2 (TXA2) during in vitro platelet aggregation induced by ADP, epinephrine, collagen, ionophore A23187 and arachidonic acid. Inhibition occurred after a short incubation (30–40 sec) and depended on the concentration of the drug or its metabolites and the aggregating agents. The minimal inhibitory concentration of dipyrone needed to completely block aggregation varied between individual donors, and related directly to the inherent capacity of their platelets to synthesize TXA2.Incubation of dipyrone with cultured bovine aortic endothelial cells resulted in a time and dose dependent inhibition of the release of prostacyclin (PGI2) into the culture medium. However, inhibition was abolished when the drug was removed from the culture, or when the cells were stimulated to produce PGI2 with either arachidonic acid or ionophore A23187.These results indicate that dipyrone exerts its inhibitory effect on prostaglandins synthesis by platelets or endothelial cells through a competitive inhibition of the cyclooxygenase system.

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