Vascular smooth muscle and nitric oxide

Zehetgruber, Manfred; Conforto, A.; Bing, Richard J.

doi:10.1016/0024-3205(93)90063-9

Cited by 12 publications

(7 citation statements)

References 12 publications

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“…NOS‐3 also was not detectable, but according to the literature, the µ‐splice variant of NOS‐1 could be constitutively expressed (41, 42, 46). As judged from the accumulating nitrite/nitrate levels only minimal NOS activity seems to be present (47). With regard to the source of • O 2 − the inhibitory effect of apocynin would point to NADPH‐oxidase, which has been detected in VSMC (48).…”

Section: Discussionmentioning

confidence: 99%

Peroxynitrite provides the peroxide tone for PGHS‐2‐dependent prostacyclin synthesis in vascular smooth muscle cells

2005

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Endotoxin-treated vascular smooth muscle cells (VSMCs) were recently shown to release high amounts of prostacyclin (PGI2) dependent on the induction of prostaglandin endoperoxide synthase-2 (PGHS-2). In contrast to endothelial PGI2-synthase, for which nitration and inhibition by peroxynitrite was reported, addition of SIN-1 as a peroxynitrite-generating system did not cause inhibition but rather doubled PGI2 release by VSMC. The hypothesis of peroxynitrite supplementing an unsaturated peroxide tone for PGHS-2 was supported by H2O2 exerting the same effect. Studies performed with purified PGHS-2 revealed maximal elevation of enzyme activity in the presence of equimolar concentrations of *NO and *O2-, which together form peroxynitrite, while excessive production of either one radical was inhibitory. Most importantly, 6-keto-PGF1alpha formation by intact VSMC depended on a nearly equimolar generation of *NO and *O2- for providing the endogenous peroxide tone. These findings, together with the observation that an excess of exogenously added *NO, as well as uric acid as a scavenger of peroxynitrite potently reduced PGI2 release, underlined the role of peroxynitrite as the dominating and rate-limiting intracellular mediator of peroxide tone in VSMC. The results allow us to postulate a new cross-talk between the *NO and the prostanoid pathways with a crucial role for peroxynitrite in providing the peroxide tone for a continuous activation of PGHS-2.

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Section: Discussionmentioning

confidence: 99%

Peroxynitrite provides the peroxide tone for PGHS‐2‐dependent prostacyclin synthesis in vascular smooth muscle cells

2005

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“…However, it remains a matter of debate whether NO production by VSMC is physiologically relevant in contractile functions. Zehetgruber et al (42) demonstrated that NO is released by VSMC as well as by the endothelium, but the amount of NO released by the smooth muscle was insufficient to relax endothelium-deprived vascular preparations of bovine pulmonary arteries. It was later found that medial cells of bovine carotid and human renal arteries (43) and media of the rat aorta (32) do generate NO in amounts sufficient to modulate vascular contractility.…”

Section: Discussionmentioning

confidence: 99%

Vascular smooth muscle and nitric oxide synthase

et al. 2002

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The concept of endothelium-derived relaxing factor (EDRF) put forward in 1980 by Furchgott and Zawadzki implies that nitric oxide (NO) produced by NO synthase (NOS) in the endothelium diffuses to the underlying vascular smooth muscle, where it modulates vascular tone as well as vascular smooth muscle cell (VSMC) proliferation by increasing cGMP formation with subsequent activation of cGMP-dependent protein kinase. According to this concept, VSMC do not express NOS by themselves. This attractive, simple scheme is now under considerable debate. To address this issue, we designed this study with the use of a novel supersensitive immunocytochemical technique of signal amplification with tyramide and electron microscopic immunogold labeling complemented with Western blotting, as in our recent studies demonstrating NOS in the myocardial and skeletal muscles. We provide the first evidence that, in contrast to the currently accepted view, VSMC in various blood vessels express all three NOS isoforms depending on the blood vessel type. These findings suggest an alternative mechanism by which local NOS expression may modulate vascular functions in an endothelium-independent manner.

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“…As already stated, NO is synthesized by NOS from L-arginine in vascular endothelial cells and exerts its vasodilator action through activation of cGMP in vascular smooth muscle cells. NO is also synthesized in the vascular smooth muscle cells, maintaining vascular smooth muscle tone (61)(62)(63).…”

Section: Validation Of the Vallance-moncada Hypothesismentioning

confidence: 99%