S-Nitrosothiols: a class of nitric oxide-donor drugs

2000 ◽  
Vol 98 (5) ◽  
pp. 507-520 ◽  
Author(s):  
Haitham AL-SA'DONI ◽  
Albert FERRO
Keyword(s):  
Nitric Oxide ◽  
The Body ◽  
Nitric Oxide Donor ◽  
Organic Nitrates ◽  
Cardiovascular Disorders ◽  
No Donor ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Cardiovascular Therapeutics

Nitric oxide (NO) was originally described as the principal endothelium-derived relaxing factor, but it is now known to subserve a variety of functions throughout the body, both physiological and pathophysiological. NO-donor drugs decompose in the body, by a variety of mechanisms, to generate NO. Such drugs have been used for many years in cardiovascular therapeutics, in particular the organic nitrates for the prevention and treatment of angina pectoris and sodium nitroprusside for the treatment of hypertensive emergencies. However, patients taking long-term nitrates often develop tolerance, and prolonged nitroprusside administration can give rise to cyanide accumulation in the body. Newer NO-donor drugs, in particular the S-nitrosothiols, offer advantages over the existing drugs, since they do not share these drawbacks, and initial small clinical studies suggest that they may be of benefit in a variety of cardiovascular disorders. Here we briefly review the chemistry and physiology of NO, and discuss the chemistry and clinical possibilities of the S-nitrosothiols.

A review of the synthesis of nitric oxide donor and donor derivatives with pharmacological activities

2021 ◽  
Vol 21 ◽  
Author(s):  
Kexin Wang ◽  
Yue Wang ◽  
Hualin Zhang ◽  
Xintong Li ◽  
Weina Han
Keyword(s):  
Nitric Oxide ◽  
The Body ◽  
Nitric Oxide Donor ◽  
Pharmacological Activities ◽  
No Donor ◽  
No Donors ◽  
Physiological Conditions ◽  
Gaseous Substance ◽  
Human Need ◽  
Endogenous Nitric Oxide

: Abstract Endogenous nitric oxide (NO) is an important effector molecule and signal transduction molecule, which participates in the regulation of multiple functions in organisms, involving a variety of physiological and pathological processes, especially playing a very important role in the cardiovascular, immune, and nervous systems. NO is a gaseous substance with a short half-life in the body and is unstable in aqueous solutions. Therefore, many researchers focus on the release and activity of NO donors and their derivatives. However, NO donors can release free NO or NO analogues under physiological conditions to meet the human need. NO donors can be coupled with the corresponding active basic nucleus, so that they have the biological activity derived from both the basic nucleus and the NO donors, thus performing better bioactivity. This paper reviewed the routes of synthesis and advance activities of NO donor derivatives.

Modulation of cerebral arterial tone by endothelium-derived relaxing factor

1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Maximum Tension ◽  
Relaxing Factor ◽  
Middle Cerebral Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone ◽  
Dose Dependent ◽  
Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

Endothelial Dysfunction in Shock States

Physiology ◽  
1993 ◽  
Vol 8 (4) ◽  
pp. 145-148 ◽  
Author(s):  
AGB Kovach ◽  
AM Lefer
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Tissue Injury ◽  
Circulatory Shock ◽  
Relaxing Factor ◽  
Vascular Beds ◽  
Endothelium Derived Relaxing Factor

Circulatory shock results in dysfunction of the endothelium in various vascular beds. This dysfunction is characterized by marked impairment in the vasculature's ability to relax to endothelium-dependent vasodilators. This loss of endothelium-derived relaxing factor, or nitric oxide, leads to profound tissue injury.

Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

1990 ◽  
Vol 258 (1) ◽  
pp. F162-F167 ◽  
Author(s):  
P. J. Shultz ◽  
A. E. Schorer ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Functional Responses ◽  
Cross Sectional ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

scholarly journals Analysis of nitric oxide donor effectiveness in resistance vessels

2005 ◽  
Vol 288 (5) ◽  
pp. H2390-H2399 ◽  
Author(s):  
Daniel R. Hyduke ◽  
James C. Liao
Keyword(s):  
Nitric Oxide ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Interstitial Space ◽  
The Body ◽  
Nitric Oxide Donor ◽  
Free Zone ◽  
Pathological Conditions ◽  
Resistance Vessels ◽  
No Bioavailability

Decreased nitric oxide (NO) bioavailability is associated with a number of pathological conditions. Administration of a supplemental source of NO can counter the pathological effects arising from decreased NO bioavailability. A class of NO-nucleophile adducts that spontaneously release NO (NONOates) has been developed, and its members show promise as therapeutic sources of NO. Because the NONOates release NO spontaneously, a significant portion of the NO may be consumed by the myriad of NO reactive species present in the body. Here we develop a model to analyze the efficacy of NO delivery, by membrane-impermeable NONOates, in the resistance arterioles. Our model identifies three features of blood vessels that will enhance NONOate efficacy: 1) the amount of NO delivered to the abluminal region increases with lumen radius; 2) the presence of a flow-induced red blood cell-free zone will augment NO delivery; and 3) extravasation of the NONOate into the interstitial space will increase abluminal NO delivery. These results suggest that NONOates may be more effective in larger vessels and that NONOate efficacy can be altered by modifying permeability to the interstitial space.

scholarly journals Impaired Modulation of Sympathetic Excitability by Nitric Oxide After Long-term Administration of Organic Nitrates in Pigs

Circulation ◽  
1998 ◽  
Vol 97 (23) ◽  
pp. 2352-2358 ◽  
Author(s):  
Johannes Zanzinger ◽  
Jürgen Czachurski ◽  
Horst Seller
Keyword(s):  
Nitric Oxide ◽  
Organic Nitrates ◽  
Term Administration
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