Release of nitric oxide from human vascular smooth muscle cells

Bernhardt, J.; Tschudi, Marcel R.; Dohi, Yasuaki; Gut, I. T.; Urwyler, Bernhard; Bühler, Fritz R.; Lüscher, Thomas F.

doi:10.1016/s0006-291x(05)81151-9

Cited by 55 publications

(25 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inducible isoforms of NO synthase can be ex pressed in a wide variety of cells, including immune cells (macrophages, T cells), endothelium, vascular smooth muscle, cardiac myocytes, and astrocytoma cells in the brain [20], Human cells are capable of expressing the inducible NO synthase, since it has been shown that nitric oxide is generated from ¿-arginine in human macro phages [24], neutrophils [25,26] and vascular smooth muscle [27], and such a protein has been cloned from human hepatocytes [28] and chondrocytes [29],…”

Section: 'Inducible' No Synthasesmentioning

confidence: 99%

Nitric Oxide in Cardiovascular Disorders

Dusting

1995

J Vasc Res

102

View full text Add to dashboard Cite

Nitric oxide derived from the vascular endothelium and other cells of the cardiovascular system has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. Nitric oxide can be synthesised from L-arginine by any of three isoforms of nitric oxide synthase (NOS), and its interaction with prostacyclin, its proposed mechanisms of action and cytotoxicity are briefly reviewed in the context of cardiovascular function. Although nitric oxide can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Nitric oxide has important roles in the physiological regulation of local blood flow and blood pressure, especially during exercise and in response to shear stresses and other local factors in arterioles. Nitric oxide is also involved in neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilatation and inflammation associated with activation of sensory nerves. In pathological circumstances, excess nitric oxide produced by inducible NOS compromises circulatory function in septic shock, during transplant rejection, and during myocardial ischaemia and reperfusion injury. Immunosuppressant drugs like cyclosporin A inhibit the expression of NOS through complex intracellular intermediates. Disturbances in the activity of constitutive and inducible NOS in the artery wall accompany the development of atherosclerosis, vasospasm and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. Reversing the nitric oxide defect with therapeutic agents including angiotensin-converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease.

show abstract

Section: 'Inducible' No Synthasesmentioning

confidence: 99%

Nitric Oxide in Cardiovascular Disorders

Dusting

1995

J Vasc Res

102

View full text Add to dashboard Cite

show abstract

“…In contrast, the iNOS system begins to generate large amounts of NO several hours after exposure to cytokines. There is recent evidence that interleukin-1 (IL-I), a macrophage-derived cytokine, stimulates the release of large amounts of NO from VSMC in vitro (16,17). Joly et al (18) also suggested that vascular smooth muscle contains a system that generates NO after balloon injury in vivo.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide mediates cytotoxicity and basic fibroblast growth factor release in cultured vascular smooth muscle cells. A possible mechanism of neovascularization in atherosclerotic plaques.

Fukuo

Inoue²,

Morimoto³

et al. 1995

J. Clin. Invest.

112

View full text Add to dashboard Cite

To define the pathophysiological role of nitric oxide (NO) released from vascular smooth muscle cells (VSMC), we examined whether NO released from VSMC induces cytotoxicity in VSMC themselves and adjacent endothelial cells (EC) using a coculture system. Prolonged incubation with interleukin-1 (IL-1) induced large amounts of NO release and cytotoxicity in VSMC. NG-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited both NO release and cytotoxicity induced by IL-1. In contrast, DNA synthesis in cocultured EC was not inhibited but rather stimulated by prolonged incubation with IL-1 or sodium nitroprusside (SNP), a NO donor. However, IL-1 and SNP did not stimulate but inhibited DNA synthesis in EC alone. On the other hand, conditioned medium from VSMC incubated for a long period with IL-1 or SNP stimulated DNA synthesis in EC alone. Furthermore, the concentration of basic fibroblast growth factor in the conditioned medium was increased and correlated with the degree of cytotoxicity in VSMC. These results indicate that NO released from VSMC induces VSMC death, which results in release of basic fibroblast growth factor, which then stimulates adjacent EC proliferation. Thus, NO released from VSMC may participate in the mechanism of neovascularization in atherosclerotic plaques. (J. Clin. Invest. 1995. 95:669-676.)

show abstract

“…NOS isoenzymes [5] have been categorized into inducible and constitutive isoforms (table I). However, it is apparent that activity of inducible NOS (iNOS) is also constitutively present in many tissues, and that a constitutively present activity of iNOS is further upregulated by enzymeinducing signals in these cell types [6][7][8]. It has also become clear that the expression and activity of the constitutive NOS (eNOS) are modulated as well [9].…”

mentioning

confidence: 99%

Nitric Oxide and Infection: Another View

Schoedon

Schneemann

Walter

et al. 1995

Clinical Infectious Diseases

View full text Add to dashboard Cite

Nitric oxide (NO) has been nicknamed "murderer" and "mediator" because it has toxic and signaling properties. We review these two aspects of NO synthesis from the perspective of the clinical infectious disease specialist by considering the potential of NO as an endothelium-derived relaxing factor (EDRF) in inflammation and sepsis and its potential as an antimicrobial system. We deviate from observations in recent authoritative reviews and point to important speciesdifferences that make it unlikely that NO serves as an EDRF mediating inflammatory vasodilatation in humans or that NO synthesized by human phagocytes has an antimicrobial function. We propose that in humans, NO synthesis is more confined and compartmentalized than in certain other animal species, and therefore, unwelcome toxicity, vasodilatation, or disturbance of paracrine signaling mechanisms (i.e., modulation of phagocytic cell functions) are avoided during inflammation.Nitric oxide (NO) has received much attention over the last few years and was named molecule of the year in 1992 [1]. The recent scientific literature is replete with articles on the many aspects of biological and pathological processes involving NO (reviewed in [2][3][4]), suggesting at times that NO might be a jack-of-all-trades. Two aspects of the generation of NO are of particular interest to infectious disease specialists: (I) the potential role of NO as a cytotoxic molecule contributing to the antimicrobial armature of phagocytes and (2) the role of NO as a vasodilator of inflammation and mediator of septic shock. We outline our view on the role of NO in infectious processes in the human system. Our view deviates in some aspects from recent authoritative analyses [2-4] and takes into account evolutionary adaptations favorable to a utilization of this highly reactive and toxic molecule, nicknamed "murderer" [3], as a mediator.NO is produced in human and laboratory animals by NO synthases (NOS). NOS isoenzymes [5] have been categorized into inducible and constitutive isoforms (table I). However, it is apparent that activity of inducible NOS (iNOS) is also constitutively present in many tissues, and that a constitutively present activity of iNOS is further upregulated by enzymeinducing signals in these cell types [6][7][8]. It has also become clear that the expression and activity of the constitutive NOS (eNOS) are modulated as well [9].NO as Antimicrobial Product of Mononuclear Phagocytes NO derived in mononuclear phagocytes by a high-output iNOS from L-arginine has been proposed to have antibacterial,

show abstract

Release of nitric oxide from human vascular smooth muscle cells

Cited by 55 publications

References 14 publications

Nitric Oxide in Cardiovascular Disorders

Nitric Oxide in Cardiovascular Disorders

Nitric oxide mediates cytotoxicity and basic fibroblast growth factor release in cultured vascular smooth muscle cells. A possible mechanism of neovascularization in atherosclerotic plaques.

Nitric Oxide and Infection: Another View

Contact Info

Product

Resources

About