Evidence for a correlation between nitric oxide formation by cleavage of organic nitrates and activation of guanylate cyclase

Schröder, H.; Noack, E.; Müller, Ronny

doi:10.1016/s0022-2828(85)80106-1

Cited by 51 publications

(19 citation statements)

References 8 publications

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“…Preservation of the spatial heterogeneity of constrictor responses in the presence of haemoglobin implies that it is primarily determined by smooth muscle responsiveness and not by EDRF activity. The effects of GTN are relevant in that its activity is dependent on biotransformation to nitric oxide (Schroder et al, 1985), so that it can therefore be regarded as an exogeneous counterpart of EDRF. GTN (at two different concentrations) dilated all generations of the preconstricted bed to an equivalent relative extent (Ad/AD, Table la,b), either in the presence or in the absence of basal EDRF activity.…”

Section: Discussionmentioning

confidence: 99%

“…We have also studied responses to acetylcholine and substance P which can mediate relaxation in isolated conduit vessel preparations through an endothelium-dependent mechanism (Furchgott, 1983;D'Orleans-Juste et al, 1985). In addition, we studied responses to glyceryl trinitrate (GTN), whose activity is thought to depend on biotransformation to nitric oxide (Schroder et al, 1985). EDRF and GTN relax vascular smooth muscle by activating soluble guanylate cyclase, elevating tissue levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP; Holzmann, 1982;Rapoport et al, 1983;Griffith et al, 1985;Forstermann et al, ©D The Macmillan Press Ltd.…”

Section: Introductionmentioning

confidence: 99%

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Endothelium‐derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear

Griffith

Edwards

Davies

et al. 1988

British J Pharmacology

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1 Microradiographic techniques have been used to show that endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide, influences vasomotor responses in small arteries and arterioles down to 25 gm in diameter in an isolated, intact, buffer-perfused ear preparation of the rabbit. Arteries down to 75 pm in diameter, i.e. the central ear artery (GO) and its first three generations of branch vessels (GI, G2 and G3) were studied quantitatively. 2 Relative constrictor responses to 1 yM 5-hydroxytryptamine (5-HT) and the combination of 1 DM 5-HT and 1 gM histamine diminished progressively from GO to G3. Constrictor responses to 5-HT were doubled in all generations by 1 M haemoglobin which abolishes EDRF activity. 3 Relative dilator responses to acetylcholine or to substance P in preconstricted arteries were, in contrast, equal in the different generations. Mean -log (IC50) values calculated from diameter measurements were 7.63 + 0.1OM and 9.80 + 0.11 M, respectively. These dilator responses were abolished by 1 yM haemoglobin, implying that they were EDRF-mediated. Spatial homogeneity of relative dilator responses was found also with glyceryl trinitrate (10 or 50 pM) whose activity is thought to depend on biotransformation to nitric oxide, in both the presence and the absence of haemoglobin. 4 This finding of spatial homogeneity of the diameter response to changes in EDRF activity (or to glyceryl trinitrate) implies that EDRF influences hydrodynamic resistance more in vessels where constrictor tone is high.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endothelium‐derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear

Griffith

Edwards

Davies

et al. 1988

British J Pharmacology

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“…To investigate the effect of various agents on mitogenesis, quiescent cells were cultured for 20 h in medium supplemented with or without 5% serum, containing or lacking experimental agents. Finally, cells were incubated for 2 h in freshly prepared media that were additionally supplemented with I uCi [methyl-3H]thymidine (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) Ci * mmol-'; New England Nuclear, Boston, MA), to measure DNA synthesis by thymidine incorporation. The …”

Section: Methodsmentioning

confidence: 99%

“…Tennessee 38163 much as EDRF increases vascular cGMP and cGMP analogues as well as agents that increase cGMP mimic the actions of EDRF (9)(10)(11)(12). In addition, pharmacologic inhibition of the increase of cGMP induced by EDRF attenuates its vasodilatory effect ( 13).…”

mentioning

confidence: 99%

Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.

Garg¹,

Hassid²

1989

J. Clin. Invest.

2,031

910

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Endothelium-derived relaxing factor has been recently identified as nitric oxide. The purpose of this study was to determine if vasodilator drugs that generate nitric oxide inhibit vascular smooth muscle mitogenesis and proliferation in culture. Three chemically dissimilar vasodilators, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate, dose-dependently inhibited serum-induced thymidine incorporation by rat aortic smooth muscle cells. Moreover, 8-bromo-cGMP mimicked the antimitogenic effect of the nitric oxide-generating drugs. The antimitogenic effect of S-nitroso-N-acetylpenicillamine was inhibited by hemoglobin and potentiated by superoxide dismutase, supporting the view that nitric oxide was the ultimate effector. Sodium nitroprusside and S-nitroso-Nacetylpenicillamine significantly decreased the proliferation of vascular smooth muscle cells. Moreover, the inhibition of mitogenesis and proliferation was shown to be independent of cell damage, as documented by several criteria of cell viability. These results suggest that endogenous nitric oxide may function as a modulator of vascular smooth muscle cell mitogenesis and proliferation, by a cGMP-mediated mechanism.

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“…An in vitro test was set up to measure the enzymatic activity of GC isolated from bovine lung or rat liver tissue (13,42). NO was measured by a difference-spectrophotometric method (13).…”

Section: Formation Of Nitric Oxide and Stimulation Of Guanylate Cyclamentioning

confidence: 99%

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

Bonn

Scharfenecker

Friehe

et al. 1998

Cardiovascular Drug Reviews

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Evidence for a correlation between nitric oxide formation by cleavage of organic nitrates and activation of guanylate cyclase

Cited by 51 publications

References 8 publications

Endothelium‐derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear

Endothelium‐derived relaxing factor (EDRF) and resistance vessels in an intact vascular bed: a microangiographic study of the rabbit isolated ear

Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells.

SP/W‐5186: A Novel Sulfhydryl‐Containing NO Donor

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