Interleukin-1 β induces the production of an L-arginine-derived relaxing factor from cultured smooth muscle cells from rat aorta

Schini, Valérie B.; Junquéro, Didier; Scott‐Burden, Timothy; Vanhoutte, Paul M.

doi:10.1016/0006-291x(91)90897-g

Cited by 104 publications

(44 citation statements)

References 16 publications

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“…In summary, this study indicates that hVSMC express not only an inducible, Ca 2+ -independent NOS activity, able to produce huge amounts of NO when stimulated by endotoxins and cytokines and therefore to induce the dramatic clinical picture of septic shock [22,23] but also a constitutive, Ca 2+ -dependent NOS activity, able to be stimulated by insulin in a few minutes. The mechanisms by which insulin activates cNOS in hVSMC need further investigation: a possible hypothesis is a covalent modification of the enzyme that would result in its activation [36], as it has been already shown for the insulin effects on the cGMP-inhibited cAMP phosphodiesterase [37].…”

Section: Discussionmentioning

confidence: 68%

“…On the other hand, it has been observed that these cells contain an inducible NOS, which is Ca 2+ /calmodulin-independent and is stimulated after hours by endotoxin, interleukin-1 and tumour necrosis factor. This NOS could be important in the pathogenesis of septic shock by a huge production of NO causing profound hypotension and hyporesponsiveness to vasoconstrictors [22,23]. Our previous studies on cGMP and cAMP production in hVSMC were done using different insulin concentrations in the range 240±1920 pmol/l, at a fixed incubation time of 120 min [8,9].…”

Section: : 831±839]mentioning

confidence: 99%

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Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3′ : 5′-cyclic monophosphate and adenosine 3′ : 5′-cyclic monophosphate concentrations

et al. 1999

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Aims/hypothesis. Insulin incubation of human vascular smooth muscle cells (hVSMC) for 120 min increases both guanosine 3¢ : 5¢-cyclic monophosphate (cGMP) and adenosine 3¢ : 5¢-cyclic monophosphate (cAMP) and these effects are blocked by inhibiting nitric oxide synthase (NOS). These data suggest that insulin activates a constitutive Ca 2+ -dependent NOS (cNOS), not described at yet in hVSMC. To test this hypothesis, we evaluated in hVSMC: i) the kinetics of the insulin-induced enhancement of the two cyclic nucleotides; ii) the ability of nitric oxide (NO) to increase both cyclic nucleotides; iii) NO involvement in the short-term influence of insulin on both cyclic nucleotides; iv) the ability of insulin to increase NO production in a few minutes; v) the presence of a cNOS activity; vi) the expression of mRNA for cNOS. Methods. In hVSMC incubated with insulin, NO donors and the Ca 2+ ionophore ionomycin, we measured cAMP and cGMP (RIA); in hVSMC incubated with insulin and ionomycin we measured NO, evaluated as l-( 3 H)-citrulline production from l-( 3 H)-arginine; by northern blot hybridization, we measured the expression of cNOS mRNA. Results. i) By incubating hVSMC with 2 nmol/l insulin for 0±240 min, we observed an increase of both cGMP and cAMP (ANOVA: p = 0.0001). Cyclic GMP rose from 0.74 ± 0.01 to 2.62 ± 0.10 pmol/10 6 cells at 30 min (p = 0.0001); cAMP rose from 0.9 ± 0.09 to 11.65 ± 0.74 pmol/10 6 cells at 15 min (p = 0.0001). ii) Sodium nitroprusside (100 mmol/l) and glyceryltrinitrate (100 mmol/l) increased both cGMP and cAMP (p = 0.0001). iii) The effects of insulin on cyclic nucleotides were blocked by NOS inhibition. iv) An increase of NO was observed by incubating hVSMC for 5 min with 2 nmol/l insulin (p = 0.0001). v) Ionomycin (1 mmol/l) enhanced NO production (p = 0.0001) and increased both cyclic nucleotides (p = 0.0001). vi) hVSMC expressed mRNA of cNOS. Conclusion/interpretation. Human VSMC express cNOS, which is rapidly activated by insulin with a consequent increase of both cGMP and cAMP, suggesting that insulin-induced vasodilation in vivo is not entirely endothelium-mediated. [Diabetologia (1999) 42: 831±839]

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Section: Discussionmentioning

confidence: 68%

Section: : 831±839]mentioning

confidence: 99%

Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3′ : 5′-cyclic monophosphate and adenosine 3′ : 5′-cyclic monophosphate concentrations

et al. 1999

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“…induces the production of a transferrable factor from cultured smooth muscle cells which relaxes vascular smooth muscle and stimulates the production of cyclic GMP (Schini et al, 1991). The stimulation of membrane receptors in NG 108-15 cells also increases cyclic GMP accumulation, an effect inhibited by pertussis toxin (Kurose & Ui, 1985) and a cell surface receptor activates Mg2+-dependent guanylate cyclase in the cellular slime mold Dictyostelium discoidenum (Janssens et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Vuorinen¹,

Pörsti²,

Metsä‐Ketelä³

et al. 1992

British J Pharmacology

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1 The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on vascular tone and cyclic nucleotide accumulation of noradrenaline-precontracted endothelium-intact and endothelium-denuded rat mesenteric artery rings were compared with the effects of the known purinoceptor agonists adenosine 5'-triphosphate (ATP) and adenosine.2 GTP (10pM-1 mM) dose-dependently relaxed endothelium-intact mesenteric artery rings by producing a rapid initial response followed by sustained relaxation resembling the relaxant response to acetylcholine. GTP also slightly relaxed endothelium-denuded artery rings. The acetylcholine-and GTP-induced relaxations of endothelium-intact rings were attenuated by NG-nitro L-arginine methyl ester (L-NAME, 330pM) which attenuation was reversed with L-arginine (1 mM). 3 Guanosine (lOuM-1 mM) relaxed both endothelium-intact and -denuded artery rings in a dosedependent manner. The relaxations were more pronounced in endothelium-intact preparations and were only slightly attenuated by L-NAME (330pM). 4 ATP (1 pM-1 mM) and adenosine (1OpM-1 mM) dose-dependently relaxed endothelium-intact and -denuded artery rings. The responses were more pronounced in endothelium-intact vascular preparations.5 GTP (100pM) and guanosine (100puM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in both endothelium-intact and -denuded artery rings corresponding to the relaxations observed. The concentrations of adenosine 3': 5'-cyclic monophosphate (cyclic AMP) were not affected. 6 ATP (100pM) increased cyclic GMP concentration of endothelium-intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100pM) and adenosine (100pM) in endothelium-intact and -denuded vascular preparations. 7 These results provide evidence that exogenous GTP and guanosine relax precontracted endotheliumintact and -denuded rat mesenteric artery rings by increasing cyclic GMP accumulation. The response to GTP of endothelium-intact rings can mainly be explained by the release of endothelium-derived relaxing factor (EDRF), but that of guanosine is only partly due to EDRF, and is a combination of endotheliumdependent and -independent effects. The endothelium-independent response of GTP and guanosine is a direct, unknown effect on smooth muscle and guanylate cyclase.

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“…It has been reported that these cytokines increase accumulation of cGMP in rabbit and rat VSMC, possibly via NO production (6,15). In endotoxin shock, it has been suggested that excessive production of NO stimulated by LPS and cytokines contributes to the development of profound hypotension and hyporesponsiveness of exogenous vasoconstrictors.…”

Section: Introductionmentioning

confidence: 99%

Induction of nitric oxide synthase by cyclic AMP in rat vascular smooth muscle cells.

Imai¹,

Hirata²,

Kanno³

et al. 1994

J. Clin. Invest.

148

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By measurements of NO /NO (NOx) production and Northern blot analysis, we studied the effects of a membranepermeable cAMP derivative, 8-bromo-cAMP, on the expression of inducible nitric oxide synthase (iNOS) gene and the synthesis of NOx in cultured rat vascular smooth muscle cells (VSMCs). 8-bromo-cAMP stimulated NOx production and increased steady-state levels of iNOS mRNA in rat VSMC in a time-and dose-dependent manner. NG-monomethyl-L-arginine, a NOS inhibitor, completely blocked the 8-bromocAMP-induced NOx production, whose effect was partially, but significantly reversed by an excess L-arginine, but not by D-arginine. Compounds that increase intracellular cAMP levels (cholera toxin, forskolin, and 3-isobutyl-1-methylxanthine), all stimulated NOx production. Dexamethasone inhibited the stimulated NOx production, as well as the induction of iNOS mRNA by cAMP. Both actinomycin D and cycloheximide completely blocked the stimulated NOx production by cAMP. Actinomycin D abolished the cAMP-induced iNOS mRNA, whereas cycloheximide remarkably increased iNOS mRNA levels in the presence and absence of 8-bromo-cAMP (superinduction). Actinomycin D, but not dexamethasone, completely abolished the cycloheximide-induced iNOS mRNA. The half-life of cAMP-induced iNOS mRNA was -2 h, whereas no decay in the cycloheximide-induced iNOS mRNA was observed during 12 h. These results demonstrate that iNOS gene is upregulated by cAMP and the superinduction of iNOS mRNA is attributable to increased mRNA stability in rat VSMC. (J. Clin. Invest. 1994. 93:543-549.)

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Interleukin-1 β induces the production of an L-arginine-derived relaxing factor from cultured smooth muscle cells from rat aorta

Cited by 104 publications

References 16 publications

Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3′ : 5′-cyclic monophosphate and adenosine 3′ : 5′-cyclic monophosphate concentrations

Human vascular smooth muscle cells express a constitutive nitric oxide synthase that insulin rapidly activates, thus increasing guanosine 3′ : 5′-cyclic monophosphate and adenosine 3′ : 5′-cyclic monophosphate concentrations

Endothelium‐dependent and ‐independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery

Induction of nitric oxide synthase by cyclic AMP in rat vascular smooth muscle cells.

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