Substrate Inhibition of Nitric Oxide Synthase in Pulmonary Artery Endothelial Cells in Culture

Nitric Oxide ◽  
1997 ◽  
Vol 1 (6) ◽  
pp. 469-475 ◽  
Author(s):  
Yunchao Su ◽  
Margaret Couch ◽  
Edward R. Block
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Substrate Inhibition ◽  
Cells In Culture ◽  
Oxide Synthase

Modulation of Inducible Nitric Oxide Synthase by Hypoxia in Pulmonary Artery Endothelial Cells

2002 ◽  
Vol 26 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Javier J. Zulueta ◽  
Raneeta Sawhney ◽  
Usamah Kayyali ◽  
Michael Fogel ◽  
Cameron Donaldson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Inducible Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Roles of accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, and attenuated nitric oxide synthase activity in endothelial cells for pulmonary hypertension in rats

2007 ◽  
Vol 292 (6) ◽  
pp. L1480-L1487 ◽  
Author(s):  
Akihito Sasaki ◽  
Shouzaburoh Doi ◽  
Shuki Mizutani ◽  
Hiroshi Azuma
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Protein Expression ◽  
No Production ◽  
Nos Inhibitors ◽  
Endogenous Nitric Oxide ◽  
Oxide Synthase

Nitric oxide (NO) has been suggested to play a key role in the pathogenesis of pulmonary hypertension (PH). To determine which mechanism exists to affect NO production, we examined the concentration of endogenous nitric oxide synthase (NOS) inhibitors and their catabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) activity and protein expression (DDAH1 and DDAH2) in pulmonary artery endothelial cells (PAECs) of rats given monocrotaline (MCT). We also measured NOS and arginase activities and NOS protein expression. Twenty-four days after MCT administration, PH and right ventricle (RV) hypertrophy were established. Endothelium-dependent, but not endothelium-independent, relaxation and cGMP production were significantly impaired in pulmonary artery specimens of MCT group. The constitutive NOS activity and protein expression in PAECs were significantly reduced in MCT group, whereas the arginase, which shares l-arginine as a common substrate with NOS, activity was significantly enhanced in PAECs of MCT group. The contents of monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), but not symmetric dimethylarginine (SDMA), were increased in PAECs of MCT group. The DDAH activity and DDAH1, but not DDAH2, protein expression were significantly reduced in PAECs of MCT group. These results suggest that the impairment of cGMP production as a marker of NO production is possibly due to the blunted endothelial NOS activity resulting from the downregulation of endothelial NOS protein, accumulation of endogenous NOS inhibitors, and accelerated arginase activity in PAECs of PH rats. The decreased overall DDAH activity accompanied by the downregulation of DDAH1 would bring about the accumulation of endogenous NOS inhibitors.

Cell growth modulates nitric oxide synthase expression in fetal pulmonary artery endothelial cells

2000 ◽  
Vol 278 (1) ◽  
pp. L131-L138 ◽  
Author(s):  
Jeannette A. Whitney ◽  
Zohre German ◽  
Todd S. Sherman ◽  
Ivan S. Yuhanna ◽  
Philip W. Shaul
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Growth ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Enzymatic Activity ◽  
Vascular Function ◽  
Enos Gene ◽  
Enos Expression ◽  
Oxide Synthase

Nitric oxide (NO), produced by endothelial (e) nitric oxide synthase (NOS), is a critical mediator of vascular function and growth in the developing lung. Pulmonary eNOS expression is diminished in conditions associated with altered pulmonary vascular development, suggesting that eNOS may be modulated by changes in pulmonary artery endothelial cell (PAEC) growth. We determined the effects of cell growth on eNOS expression in cultured ovine fetal PAEC studied at varying levels of confluence. NOS enzymatic activity was sixfold greater in quiescent PAEC at 100% confluence compared with more rapidly replicating cells at 50% confluence. To determine if there is a reciprocal effect of NO on PAEC growth, studies of NOS inhibition or the provision of exogenous NO from spermine NONOate were performed. Neither intervention had a discernable effect on PAEC growth. The influence of cell growth on NOS activity was unique to pulmonary endothelium, because varying confluence did not alter NOS activity in fetal systemic endothelial cells. The effects of cell growth induced by serum stimulation were also evaluated, and NOS enzymatic activity was threefold greater in quiescent, serum-deprived cells compared with that in serum-stimulated cells. The increase in NOS activity observed at full confluence was accompanied by parallel increases in eNOS protein and mRNA expression. These findings indicate that eNOS gene expression in fetal PAEC is upregulated during cell quiescence and downregulated during rapid cell growth. Furthermore, the interaction between cell growth and NO in the PAEC is unidirectional.

Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor

2004 ◽  
Vol 287 (3) ◽  
pp. L559-L568 ◽  
Author(s):  
Susan Olson ◽  
Richard Oeckler ◽  
Xinmei Li ◽  
Litong Du ◽  
Frank Traganos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Oxide Synthase

We previously reported that angiotensin II stimulates an increase in nitric oxide production in pulmonary artery endothelial cells. The aims of this study were to determine which receptor subtype mediates the angiotensin II-dependent increase in nitric oxide production and to investigate the roles of the angiotensin type 1 and type 2 receptors in modulating angiotensin II-dependent vasoconstriction in pulmonary arteries. Pulmonary artery endothelial cells express both angiotensin II type 1 and type 2 receptors as assessed by RT-PCR, Western blot analysis, and flow cytometry. Treatment of the endothelial cells with PD-123319, a type 2 receptor antagonist, prevented the angiotensin II-dependent increase in nitric oxide synthase mRNA, protein levels, and nitric oxide production. In contrast, the type 1 receptor antagonist losartan enhanced nitric oxide synthase mRNA levels, protein expression, and nitric oxide production. Pretreatment of the endothelial cells with either PD-123319 or an anti-angiotensin II antibody prevented this losartan enhancement of nitric oxide production. Angiotensin II-dependent enhanced hypoxic contractions in pulmonary arteries were blocked by the type 1 receptor antagonist candesartan; however, PD-123319 enhanced hypoxic contractions in angiotensin II-treated endothelium-intact vessels. These data demonstrate that angiotensin II stimulates an increase in nitric oxide synthase mRNA, protein expression, and nitric oxide production via the type 2 receptor, whereas signaling via the type 1 receptor negatively regulates nitric oxide production in the pulmonary endothelium. This endothelial, type 2 receptor-dependent increase in nitric oxide may serve to counterbalance the angiotensin II-dependent vasoconstriction in smooth muscle cells, ultimately regulating pulmonary vascular tone.

scholarly journals Interaction of endothelial nitric oxide synthase with mitochondria regulates oxidative stress and function in fetal pulmonary artery endothelial cells

2015 ◽  
Vol 309 (9) ◽  
pp. L1009-L1017 ◽  
Author(s):  
Girija G. Konduri ◽  
Adeleye J. Afolayan ◽  
Annie Eis ◽  
Kirkwood A. Pritchard ◽  
Ru-Jeng Teng
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Pulmonary Arteries ◽  
Mitochondrial Outer Membrane ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

An increase in oxygen tension at birth is one of the key signals that initiate pulmonary vasodilation in the fetal lung. We investigated the hypothesis that targeting endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane regulates reactive oxygen species (ROS) formation in the fetal pulmonary artery endothelial cells (PAEC) during this transition. We isolated PAEC and pulmonary arteries from 137-day gestation fetal lambs (term = 144 days). We exposed PAEC to a simulated transition from fetal to (3% O2) to normoxic (21%) or hyperoxic (95% O2) postnatal Po2 or to the nitric oxide synthase (NOS) agonist ATP. We assessed the effect of O2 and ATP on eNOS interactions with the mitochondrial outer membrane protein porin and with the chaperone hsp90. We also investigated the effect of decoy peptides that blocked eNOS interactions with porin or hsp90 on PAEC angiogenesis and vasodilator function of pulmonary arteries. Transition of fetal PAEC from 3 to 21% O2 but not to 95% O2 or exposure to ATP increased eNOS association with hsp90 and porin. Decoy peptides that blocked eNOS interactions decreased NO release, increased O2 consumption and mitochondrial ROS levels, and impaired PAEC angiogenesis. Decoy peptides also inhibited the relaxation responses of pulmonary artery rings and dilation of resistance size pulmonary arteries to ATP. The mitochondrial-antioxidant mito-ubiquinone restored the response to ATP in decoy peptide-treated pulmonary arteries. These data indicate that targeting eNOS to mitochondria decreases endothelial oxidative stress and facilitates vasodilation in fetal pulmonary circulation at birth.

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