Blood Vessel Specific Vaso-Activity To Nitrite Under Normoxic And Hypoxic Conditions

Ingram, Thomas E.; Pinder, Andrew G.; Milsom, Alexandra; Rogers, Stephen C.; Thomas, Deepak; James, Philip E.

doi:10.1007/978-0-387-85998-9_4

Cited by 8 publications

(7 citation statements)

References 3 publications

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“…Under normoxic conditions, the pulmonary artery dilated more than the aorta (the inferior vena cava response was variable). However, under conditions of hypoxia, dilatation of the aorta was significantly greater than of the pulmonary artery and the inferior vena cava . The dilatory response during hypoxia was enhanced in all vascular beds.…”

Section: Cardiovascular Effects Of Nitrate and Nitritementioning

confidence: 84%

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases

et al. 2015

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Abstract. Omar SA, Webb AJ, Lundberg JO, Weitzberg E (Karolinska Institutet, Stockholm, Sweden; and King's College London British Heart Foundation Centre, London, UK). Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases (Review). J Intern Med 2016; 279: 315-336.Nitric oxide (NO) is generated endogenously by NO synthases to regulate a number of physiological processes including cardiovascular and metabolic functions. A decrease in the production and bioavailability of NO is a hallmark of many major chronic diseases including hypertension, ischaemia-reperfusion injury, atherosclerosis and diabetes. This NO deficiency is mainly caused by dysfunctional NO synthases and increased scavenging of NO by the formation of reactive oxygen species. Inorganic nitrate and nitrite are emerging as substrates for in vivo NO synthase-independent formation of NO bioactivity. These anions are oxidation products of endogenous NO generation and are also present in the diet, with green leafy vegetables having a high nitrate content. The effects of nitrate and nitrite are diverse and include vasodilatation, improved endothelial function, enhanced mitochondrial efficiency and reduced generation of reactive oxygen species. Administration of nitrate or nitrite in animal models of cardiovascular disease shows promising results, and clinical trials are currently ongoing to investigate the therapeutic potential of nitrate and nitrite in hypertension, pulmonary hypertension, peripheral artery disease and myocardial infarction. In addition, the nutritional aspects of the nitratenitrite-NO pathway are interesting as diets suggested to protect against cardiovascular disease, such as the Mediterranean diet, are especially high in nitrate. Here, we discuss the potential therapeutic opportunities for nitrate and nitrite in prevention and treatment of cardiovascular and metabolic diseases.

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Section: Cardiovascular Effects Of Nitrate and Nitritementioning

confidence: 84%

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases

et al. 2015

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“…It has been shown that even in the absence of added heme, nitrite induces vasorelaxation at high and low oxygen tensions via NO formation [21; 22; 48; 49]. As a result, the addition of either bHb or THb would be expected to lead to inhibition of nitrite-dependent responses.…”

Section: Resultsmentioning

confidence: 99%

Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling

Cantú‐Medellín¹,

Vitturi²,

Rodriguez³

et al. 2011

Nitric Oxide

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Recent data suggest that transitions between the relaxed (R) and tense (T) state of hemoglobin control the reduction of nitrite to nitric oxide (NO) by deoxyhemoglobin. This reaction may play a role in physiologic NO homeostasis and be a novel consideration for the development of the next generation of hemoglobin-based blood oxygen carriers (HBOCs, i.e. artificial blood substitutes). Herein we tested the effects of chemical stabilization of bovine hemoglobin in either the T-(THb) or R-state (RHb) on nitrite reduction kinetics, NO-gas formation and ability to stimulate NOdependent signaling. These studies were performed over a range of fractional saturations that is expected to mimic biological conditions. The initial rate for nitrite-reduction decreased in the following order RHb > bHb > THb, consistent with the hypothesis that the rate constant for nitrite reduction is faster with R-state Hb and slower with T-state Hb. Moreover, RHb produced more NO-gas and inhibited mitochondrial respiration more potently than both bHb and THb. Interestingly, at low oxygen fractional saturations, THb produced more NO and stimulated nitritedependent vasodilation more potently than bHb despite both derivatives having similar initial rates for nitrite reduction and a more negative reduction potential in THb versus bHb. These data suggest that cross-linking of bovine hemoglobin in the T-state conformation leads to a more effective coupling of nitrite reduction to NO-formation. Our results support the model of allosteric regulation of nitrite reduction by deoxyhemoglobin and show that cross-linking hemoglobins in Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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“…[26][27][28] Therefore, it is possible that the Ru-NO + donates NO, whereas the configuration Ru-NO 2 2 may donate NO 2 2 or generate NO. [26][27][28] Therefore, it is possible that the Ru-NO + donates NO, whereas the configuration Ru-NO 2 2 may donate NO 2 2 or generate NO.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Vasodilating Effect Induced by the Ruthenium Complex cis-[Ru(NO)(NO2)(bpy)2].(PF6)2

Rodrigues

Pereira

Moraes

et al. 2015

Journal of Cardiovascular Pharmacology

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Nitric oxide (NO) can be found in different species and is a potent vasodilator. The ruthenium compound cis-[Ru(NO)(NO2)(bpy)2].(PF6)2 (BPY) can generate NO. This study aimed to investigate the BPY stability at physiological pH, the cellular mechanisms involved in BPY effect, NO species originating from BPY, and to verify how BPY affects blood pressure. Our results has shown that at pH 7.4 and 9.4, the NO coordinated to ruthenium (Ru-NO) is converted to nitrite (Ru-NO2) and remains stable. In aortic rings, the stable configuration of BPY (Ru-NO2) induces vascular relaxation in a concentration-dependent manner. Thus, further experiments were made with stable configuration of BPY (Ru-NO2). The relaxation induced by BPY was abolished in the presence of guanylyl cyclase inhibitor and decreased in the presence of potassium channel blocker. By using radicalar (NO) and nitroxyl (NO) scavenger, our results suggest that the BPY mainly release the radicalar species. By using fluorescence probes to detect intracellular NO concentration ([NO]i) and cytosolic Ca concentration ([Ca]c), we verified that in smooth muscle cells, BPY induces an increase in [NO]i and a decrease in [Ca]c. The intravenous bolus injection of 1.25, 2.5, and 5.0 mg/kg from stable configuration of BPY results in a decrease on basal blood pressure values. Taken together, our results indicated that the stable configuration of the compound BPY induces vascular relaxation in aorta because of NO release and decrease of [Ca]c in vascular smooth muscle cells. Also, the stable configuration is able to reduce the blood pressure in a dose-dependent manner.

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Blood Vessel Specific Vaso-Activity To Nitrite Under Normoxic And Hypoxic Conditions

Cited by 8 publications

References 3 publications

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases

Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases

Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling

Pharmacological Characterization of the Vasodilating Effect Induced by the Ruthenium Complex cis-[Ru(NO)(NO2)(bpy)2].(PF6)2

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