Mechanism of Nitric Oxide–Induced Vasodilatation

Cohen, Richard A.; Weisbrod, Robert M.; Gericke, Marion; Yaghoubi, Mohammad Ali; Bierl, Charlene; Bolotina, Victoria M.

doi:10.1161/01.res.84.2.210

Cited by 260 publications

(68 citation statements)

References 25 publications

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“…Because there was no effect on IP 3 levels, the possibility that NO may regulate either the intracellular response to IP 3 or processes of Ca 2ϩ influx and reuptake should be considered. In smooth muscle cells, NO was recently shown to influence the uptake of Ca 2ϩ by its effect on sarcoplasmic reticulum ATPase (25). It is noted that concentrations of Ang II (10 Ϫ8 M) that produce submaximal increases in IP 3 levels at the time point we used (20 s) did produce a maximal response with regard to ERK activation (9).…”

Section: Discussionmentioning

confidence: 91%

Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels

Wang

Cohen

et al. 2000

Journal of Biological Chemistry

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These studies describe inhibitory effects of N-acetylcysteine on several biochemical events associated with the activation of extracellular signal-regulated kinases (ERK) by angiotensin II in the cardiac fibroblast and compare these effects with those of the nitric oxide donor, S-nitroso-N-acetylpenicillamine, an agent we showed previously to inhibit angiotensin II-induced ERK activation and the concomitant phosphorylation of proline-rich tyrosine kinase 2 (Wang, D., Yu, X., and Brecher, P. (1999) J. Biol. Chem. 274, 24342-24348). The transactivation of the epidermal growth factor receptor by angiotensin II, a process required for the activation of ERK, was inhibited by N-acetylcysteine but not by nitric oxide. The transactivation of the epidermal growth factor receptor by angiotensin II was shown to be independent of intracellular calcium increases. Nitric oxide, but not N-acetylcysteine, inhibited the angiotensin II-induced increase in intracellular Ca 2؉. Neither nitric oxide nor N-acetylcysteine inhibited either phospholipase C activation or inositol triphosphate generation in response to angiotensin II. N-Acetylcysteine did inhibit the phosphorylation of the calcium sensitive tyrosine kinases PYK2 and Src, effects that also occurred using nitric oxide. These studies describe a novel effect of N-acetylcysteine on cross-talk between a G proteinlinked receptor and a tyrosine kinase receptor and offer additional molecular insight to explain how N-acetylcysteine and nitric oxide act at different sites and might have an additive effect on specific hormonal responses.The diverse response of target cells to angiotensin II (Ang II) 1 with respect to activation of signaling pathways has been well documented. Most studies have focused on either the vascular smooth muscle cell or the cardiac fibroblast to dilineate the intracellular steps involved in the activation of the MAP kinase system, a characteristic response now associated with hypertrophy, proliferation, or apoptosis (1-3). This kinase cascade has been shown to be under complex regulation, and its activation by Ang II has been used as a model for the study of how G protein-linked receptors can influence systems normally activated by tyrosine kinase-linked receptors (4 -6). One suggested mechanism for this response was proposed to be the transactivation of the EGF receptor by Ang II and the requirement for that receptor tyrosine kinase in the ultimate activation of MAP kinases (7,8).In a preceding study (9), we have characterized the acute activation of MAP kinases in quiescent cardiac fibroblasts by Ang II, and shown that nitric oxide (NO), a substance known to functionally oppose the physiological effects of Ang II in several organ systems, including the heart (10), can attenuate the activation of ERK by Ang II. This effect of NO on ERK activation also occurred in the same cell type when either of the other major MAP kinases (JNK or p38) were activated by Ang II, suggesting regulation at a site, or sites, upstream of Ras or proteins within the Ras superfamil...

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Section: Discussionmentioning

confidence: 91%

Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels

Wang

Cohen

et al. 2000

Journal of Biological Chemistry

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“…Cells-Primary culture SMC from mouse (mSMC) and rabbit (rSMC) aorta were prepared as described previously (10,25). Human platelets were prepared from the platelet-rich plasma as described previously (26).…”

Section: Methodsmentioning

confidence: 99%

“…Representative I/V relationships are shown during ramp depolarization after 10 min of cell dialysis. Passive leakage current with zero reversal potential (at the moment of breaking into the cell) was subtracted (it was usually higher in cells pretreated with BEL for 30 min and did not change over time (10,11,25). For summary data, ⌬ratio was calculated as the difference between the peak ratio after extracellular Ca 2ϩ was added, and its level right before Ca 2ϩ addition.…”

Section: Methodsmentioning

confidence: 99%

Ca2+-independent Phospholipase A2 Is a Novel Determinant of Store-operated Ca2+ Entry

Smani

Zakharov

Leno

et al. 2003

Journal of Biological Chemistry

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“…NO attenuates IICR at several steps, by inhibiting G-protein in VSMCs (21) and platelets (22), by inhibiting phospholipase ␤ in PC12 cells (23), and by inhibiting IP 3 receptors in VSMCs (24). The effects of NO on CCE vary among cell types (19,20,(25)(26)(27)(28)(29)(30); NO potentiates CCE in pancreatic acinar cells (25)(26)(27) and colonic epithelial cells (28), does not affect CCE in Jurkat T-lymphocytes (29) and embryonic kidney cells (30), and inhibits CCE in platelets (31) and VSMCs (32). Regarding the effects on Ca 2ϩ i sequestration, NO potentiates PMCA (33,34), NCX (35)(36)(37), and SERCA (32) in VSMCs, platelets, and astrocytes.…”

Section: Elevation No Also Potentiated Camentioning

confidence: 99%

“…The effects of NO on CCE vary among cell types (19,20,(25)(26)(27)(28)(29)(30); NO potentiates CCE in pancreatic acinar cells (25)(26)(27) and colonic epithelial cells (28), does not affect CCE in Jurkat T-lymphocytes (29) and embryonic kidney cells (30), and inhibits CCE in platelets (31) and VSMCs (32). Regarding the effects on Ca 2ϩ i sequestration, NO potentiates PMCA (33,34), NCX (35)(36)(37), and SERCA (32) in VSMCs, platelets, and astrocytes. However, in ECs, the effect of NO on Ca homeostasis varied among NO donor, NO gas, and endogenous NO, even in the same cell type (19,20,34,38,39).…”

Section: Elevation No Also Potentiated Camentioning

confidence: 99%

Autocrine Action and Its Underlying Mechanism of Nitric Oxide on Intracellular Ca2+ Homeostasis in Vascular Endothelial Cells

Chen¹,

Wang²,

Wang³

et al. 2000

Journal of Biological Chemistry

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Mechanism of Nitric Oxide–Induced Vasodilatation

Cited by 260 publications

References 25 publications

Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels

Distinct Effects of N-Acetylcysteine and Nitric Oxide on Angiotensin II-induced Epidermal Growth Factor Receptor Phosphorylation and Intracellular Ca2+ Levels

Ca2+-independent Phospholipase A2 Is a Novel Determinant of Store-operated Ca2+ Entry

Autocrine Action and Its Underlying Mechanism of Nitric Oxide on Intracellular Ca2+ Homeostasis in Vascular Endothelial Cells

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