Role of blood and vascular smooth muscle in the vasoactivity of nitrite

Liu, Taiming; Schroeder, Hobe; Barcelo, Lisa; Bragg, Shannon; Terry, Michael H.; Wilson, Sean; Power, Gordon G.; Blood, Arlin B.

doi:10.1152/ajpheart.00138.2014

Cited by 12 publications

(25 citation statements)

References 39 publications

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“…Indeed, in this study, approximately half of the L-cysNO and GSNO disappearance was accounted for by increases in plasma nitrite to concentrations of ~0.4 μmol/L. We have recently reported, however, that in sheep nitrite is a poor vasodilator even at concentrations orders of magnitude greater than those observed in the present study[22, 56]. Thus it seems more likely that the vasodilation observed in this study was not due to increases in circulating nitrite.…”

Section: Discussioncontrasting

confidence: 71%

“…The surgical procedures were reported before[22] and described in the supplemental methods. The conductances of both ipsilateral and contralateral (non-infused) femoral artery were recorded during a stable baseline period and then while L-cysNO, D-cysNO, or GSNO were infused into one (ipsilateral) femoral artery at rates of 0.2, 0.4, 0.6, and 0.8 ml/min, increasing every three minutes, Blood samples were collected from the ipsilateral femoral vein and the brachial artery before and at the end of each infusion period.…”

Section: Methodsmentioning

confidence: 99%

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Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols

Liu

Schroeder

Wilson

et al. 2016

Free Radical Biology and Medicine

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S-nitrosothiols (SNOs) such as S-nitroso-L-cysteine (L-cysNO) are endogenous compounds with potent vasodilatory activity. During circulation in the blood, the NO moiety can be exchanged among various thiol-containing compounds by S-transnitrosylation, resulting in SNOs with differing capacities to enter the cell (membrane permeability). To determine whether the vasodilating potency of SNOs is dependent upon membrane permeability, membrane-permeable L-cysNO and impermeable S-nitroso-D-cysteine (D-cysNO) and S-nitroso-glutathione (GSNO) were infused into one femoral artery of anesthetized adult sheep while measuring bilateral femoral and systemic vascular conductances. L-cysNO induced vasodilation in the infused hind limb, whereas D-cysNO and GSNO did not. L-cysNO also increased intracellular NO in isolated arterial smooth muscle cells, whereas GSNO did not. The infused SNOs remained predominantly in a low molecular weight form during first-passage through the hind limb vasculature, but were converted into high molecular weight SNOs upon systemic recirculation. At systemic concentrations of ~0.6 μmol/L, all three SNOs reduced mean arterial blood pressure by ~50%, with pronounced vasodilation in the mesenteric bed. Pharmacokinetics of L-cysNO and GSNO were measured in vitro and in vivo and correlated with their hemodynamic effects, membrane permeability, and S-transnitrosylation. These results suggest local vasodilation by SNOs in the hind limb requires membrane permeation, whereas systemic vasodilation does not. The systemic hemodynamic effects of SNOs occur after equilibration of the NO moiety amongst the plasma thiols via S-transnitrosylation.

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Section: Discussioncontrasting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols

Liu

Schroeder

Wilson

et al. 2016

Free Radical Biology and Medicine

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“…The fact, that NO release was only transient (peak) and did not reach a constant plateau suggests that NO is able to leave the RBCs and can be detected by NOA, but at the same time also binds to Hb, inhibiting its NR capacity leading to a swift decrease in NO-formation. This very short time of NO release from RBCs may be the reason that it was not observed by others 31 , 32 in similar in vitro settings. In addition, the chemiluminescence-based technique used here is very sensitive.…”

Section: Discussionmentioning

confidence: 59%

Impact of mitochondrial nitrite reductase on hemodynamics and myocardial contractility

Dungel

Penzenstadler

Ashmwe

et al. 2017

Sci Rep

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Inorganic nitrite (NO2 −) can be reduced back to nitric oxide (NO) by several heme proteins called nitrite reductases (NR) which affect both the vascular tonus and hemodynamics. The objective of this study was to clarify the impact of several NRs on the regulation of hemodynamics, for which hemodynamic parameters such as heart rate, blood pressure, arterial stiffness, peripheral resistance and myocardial contractility were characterized by pulse wave analysis. We have demonstrated that NO2 − reduced to NO in RBCs predominantly influences the heart rate, while myoglobin (Mb) and mitochondria-derived NO regulates arterial stiffness, peripheral resistance and myocardial contractility. Using ex vivo on-line NO-detection, we showed that Mb is the strongest NR occurring in heart, which operates sufficiently only at very low oxygen levels. In contrast, mitochondrial NR operates under both hypoxia and normoxia. Additional experiments with cardiomyocytes suggested that only mitochondria-derived generation of NO regulates cGMP levels mediating the contractility of cardiomyocytes. Our data suggest that a network of NRs is involved in NO2 − mediated regulation of hemodynamics. Oxygen tension and hematocrit define the activity of specific NRs.

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“…Side-by-side comparisons available from the literature show that in normoxia the vasodilating potencies of SNO are markedly greater than that of nitrite [42; 43; 44; 45; 46; 47]. Thus, the extent to which hydrophobic phases in the vascular lumen might alter the vasoactivity of NO and contribute to endothelial dysfunction in vivo should be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Although nitrate is of physiological relevance via its conversion to nitrite by commensal bacteria in the mouth, it is inert in mammalian cells [38] and thus the bioactivity of NO is lost upon conversion to nitrate. In contrast, both nitrite [39; 40; 41] and especially SNO [42; 43; 44; 45; 46; 47] are potent vasodilators. Yet, despite much interest in their bioactivity (see review by Lundberg and Weitzberg, 2010 [38]), relatively little is known about how these NO metabolites are produced in plasma.…”

Section: Introductionmentioning

confidence: 99%

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

et al. 2016

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Nitric oxide (NO) and O2 are both three- to four-fold more soluble in biological lipids than in aqueous solutions. Their higher concentration within plasma lipids accelerates NO autoxidation to an extent that may be of importance to overall NO bioactivity. This study was undertaken to test the hypothesis that increased plasma lipids after a high-fat meal appreciably accelerate NO metabolism and alter the byproducts formed. We found that plasma collected from subjects after consumption of a single high-fat meal had a higher capacity for NO consumption and consumed NO more rapidly compared to fasting plasma. This increased NO consumption showed a direct correlation with plasma triglyceride concentrations (p=0.006). The accelerated NO consumption in postprandial plasma was reversed by removal of the lipids from the plasma, was mimicked by the addition of hydrophobic micelles to aqueous buffer, and could not be explained by the presence of either free hemoglobin or ceruloplasmin. The products of NO consumption were shifted in postprandial plasma, with 55% more nitrite (n=12, p=0.002) but 50% less SNO (n=12, p=0.03) production compared to matched fasted plasma. Modeling calculations indicated that NO autoxidation was accelerated by about 48-fold in the presence of plasma lipids. We conclude that postprandial triglyceride-rich lipoproteins exert a significant influence on NO metabolism in plasma.

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Role of blood and vascular smooth muscle in the vasoactivity of nitrite

Cited by 12 publications

References 39 publications

Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols

Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols

Impact of mitochondrial nitrite reductase on hemodynamics and myocardial contractility

Postprandial lipids accelerate and redirect nitric oxide consumption in plasma

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