Mechanisms of Action of Nitrates

Torfgård, Kristina; Ahlner, Johan

doi:10.1007/978-1-4613-1135-5_2

Cited by 34 publications

(47 citation statements)

References 178 publications

(156 reference statements)

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“…The anti-ADP data point out that the (ONO2)-alkyl carbamate derivatives 5a-e showed at least a 1.6-fold loss of antiplatelet potency over the respective parent compounds 1 and 2, proving to be in vitro weak-to-moderate antiplatelet agents. Actually, the loss of antiaggregatory potency observed is not surprising, taking into account that in general alkyl nitrates decompose very slowly in plasma and buffer solution (Jones et al, 2009;Torfgard and Ahlner, 1994;Weber et al, 1993;Wendt, 1972). Whatever the rate of hydrolytic cleavage of the carbamates 5a-e in plasma to 32 eventually yield the antiplatelet compounds 1 and 2, and the (ONO2)-substituted alcohol metabolites, the experimental results led us to rule out any significant contribution of NO release to the antiplatelet activity of the tested nitrates.…”

Section: Vasodilator and Antiplatelet Activitiesmentioning

confidence: 99%

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

Candia

Marini

Zaetta

et al. 2015

European Journal of Pharmaceutical Sciences

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A number of new nitric oxide (NO)-precursors were synthesized by grafting nitrate-containing moieties on the structures of the benzyloxy isonipecotanilide derivatives 1 and 2 already reported as moderately potent antiplatelet agents. Various nitrooxy (ONO2)-alkyl side chains were covalently linked to the piperidine nitrogen of the parent compounds through carbamate and amide linkage, and the synthesis of a benzyl nitrate analog (15) of compound 1 was also achieved. The in vitro vasodilatory activities, as well as platelet anti-aggregatory effects, of the newly synthesized organic nitrates were assessed. The (ONO2)methyl carbamate-based derivative 5a and the benzyl nitrate analog 15, which on the other hand retain activity as inhibitors of ADP-induced platelet aggregation, exhibited strong NO-mediated vasodilatory effects on pre-contracted rat aorta strips, with EC50 values in the low nanomolar range (13 and 29 nM, respectively). Experiments carried out with the selectively inhibited soluble guanylate cyclase (sGC), which is the key enzyme of the NO-mediated pathway leading to vascular smooth muscle relaxation, confirmed the involvement of NO in the observed vasodilation. The nitrate derivatives proved to be stable in acidic aqueous solution and at pH 7.4. In human serum, unlike 5a, which showed not to undergo enzyme-catalyzed decomposition, the other tested (ONO2)-alkyl carbamate-based compounds (5b and 5e) and benzyl nitrate 15 underwent a faster degradation. However, their decomposition rates in serum were quite slow (t½ > 2.6 h), which suggests that nitrate moiety is poorly metabolized in blood plasma and that much of the in vitro antiplatelet activity has to be attributed to the intact (ONO2)-containing molecules.

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Section: Vasodilator and Antiplatelet Activitiesmentioning

confidence: 99%

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

Candia

Marini

Zaetta

et al. 2015

European Journal of Pharmaceutical Sciences

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“…There is continuous, basal synthesis of NO to relax VSMCs and maintain vasodilatory tone in vessels, with most of its effects exerted in the arterial rather than venous system. Pharmacological agents such as glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) exert their effects via cGMP-dependent mechanisms after conversion into NO [32]. Indeed, the benefi cial effects of ACE-I may be related, in part, to amplifi cation of the actions of bradykinin, which potentiates NO release.…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Mechanisms involved in regulation of Systemic Blood Pressure

Patel¹,

Ali²

2017

Arch Clin Hypertens

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SUMMARYRegulation of the circulatory system to maintain a constant arterial pressure is critical in ensuring adequate perfusion to meet metabolic requirements of tissues. Blood pressure (BP) can be considered in the context of Ohm's law, whereby BP (analogous to voltage) is directly proportional to the product of cardiac output (current) and total vascular resistance (TPR). Acute regulatory mechanisms are coordinated in the cardiovascular control centres in the brainstem, which are themselves infl uenced by impulses from other neural centres in addition to sensors both intrinsic and extrinsic to the circulation. However, certain organs such as the heart, kidneys and brain have the ability to coordinate blood fl ow locally, i.e. autoregulate. This enables alterations in regional perfusion without perturbations of BP. This mini-review provides an exploratory discussion of neural and humoral mechanisms that underpin regulation of systemic BP. Compared with skeletal muscle, they contract more slowly but generate higher forces with sustainable activity. Cell-to-cell conduction is via gap junctions as occurs in the myocardium. Mini Review Mechanisms involved in regulation of Systemic Blood PressureThe interaction between actin and myosin leading to contraction is regulated by intracellular calcium concentration as with other muscle, but the molecular mechanism differs [8].VSMCs lack troponin and fast sodium channels. The increase in intracellular calcium concentration arises from voltage-gated channels and receptor-mediated channels in the sarcolemma, with additional release from the sarcoplasmic reticulum (SR).Agents that can mediate effects via agonism or antagonism of these pathways include nitric oxide (NO), acetylcholine (Ach),

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“…While nitrates have a direct relaxing effect on smooth muscle cells of the vascular wall (17), Ach dilate normal arteries by promoting release of a vasorelaxing substance from the endothelium (endothelium-derived relaxing factor); conversely, if the endothelium is removed or damaged experimentally, Ach provoke vasoconstriction (18). In order to assess vasomotion, an intracoronary bolus injection of nitroglycerine (200 μg) is usually administered through the guiding catheter with two angiograms, one before and another after nitrate administration.…”

Section: Vasomotionmentioning

confidence: 99%

Methods to assess bioresorbable vascular scaffold devices behaviour after implantation

et al. 2017

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Bioresorbable vascular scaffolds (BRS) represent a novel approach for coronary revascularization offering several advantages as compared to current generation DES, potentially reducing rate of late adverse events and avoiding permanent vessel caging. Nevertheless, safety concerns have been raised for an increased risk of scaffold thrombosis (ScT) in both early and late phases, probably related to a suboptimal scaffold implantation. In this context, the use of different imaging methodologies has been strongly suggested in order to guarantee an optimal implantation. We herein analyze the different imaging methodologies available to assess BRS after implantation and at follow-up. J Thorac Dis 2017;9(Suppl 9):S959-S968 jtd.amegroups.com for BRS implantation in order to confirm optimal scaffold expansion, to exclude edge dissections, struts malapposition or underexpansion. Furthermore, imaging technique may evaluate at follow-up scaffold reabsorption and vessel changes over time. Keywords: Scaffold; intravascular ultrasound (IVUS); echogenicity; virtual histology-IVUS (VH-IVUS); optical coherence tomography (OCT); multislice coronary tomography (MSCT)SubmittedWe herein analyze the different imaging methodologies available to assess BRS after implantation and at follow-up. Quantitative coronary angiography (QCA)Coronary angiography is the most important method for assessing BRS implantation. As well as for conventional stent, at least two different projections with at least 30° difference for the right coronary artery and 3 different projections with at least 30° difference for the left coronary artery must be acquired before and after BRS implantation. The treated segment and the 5 mm proximal and distal to scaffold edges should be analyzed. As the bioresorbable devices are radiolucent, the QCA analysis may be performed visualizing the metallic markers of the scaffold.The following parameters can be measured. Acute recoilIt is defined as the difference between the mean diameter of the BRS delivery balloon (or, in case of post-dilatation, mean diameter of post-dilatation balloon) at the highest pressure and the mean lumen diameter (MLD) of the stented segment after balloon deflation. It can be expressed as absolute or relative value. The acute recoil is an important parameter in relation to the success of a PCI in acute and long-time period, as it has a direct impact on minimum stent area (MSA). A MSA less than 5.0 mm 2 is associated with high probability of in-stent restenosis (6).T h e a c u t e r e c o i l o f A b s o r b B V S 1 . 1 ( A b b o t t Laboratories, Abbott park, Illinois, USA) in the Absorb Cohort B trials and DESolve Nx BRS (Elixir Medical, Sunnyvale, California, USA) were 6.7%±6.4% and 6.4%±4.6%, respectively (7,8). These values are not dissimilar to those of metallic stent, showed in a Japanese study of 154 lesions comparing the biolimus eluting stent (Nobori stent, Terumo, Tokyo, Japan), cobalt chromium everolimus eluting stent (Xience V stent, Abbott Vascular, Santa Clara, CA, USA) and pl...

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Mechanisms of Action of Nitrates

Cited by 34 publications

References 178 publications

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

New organic nitrate-containing benzyloxy isonipecotanilide derivatives with vasodilatory and anti-platelet activity

Mechanisms involved in regulation of Systemic Blood Pressure

Methods to assess bioresorbable vascular scaffold devices behaviour after implantation

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