Cardiorespiratory effects induced by 2-nitrate-1,3-dibuthoxypropan are reduced by nitric oxide scavenger in rats

Queiroz, Thyago M.; Mendes-Júnior, Leônidas G.; Guimarães, Drielle D.; França-Silva, Maria S.; Nalivaiko, Eugene; Braga, Valdir A.

doi:10.1016/j.autneu.2013.12.012

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…Cardiovascular disease, including hypertension, is the main cause of death worldwide, and the therapeutic value of new strategies to increase NO signaling in the cardiovascular system have previously been discussed [35] . Several NO donors and organic nitrates have been studied in the past [16] , [17] , [18] , [19] , [20] , [21] , [22] , but have been associated with adverse effects mainly due to short half-life and unspecific location for NO release, as well as the development of tolerance with repeated dosing [35] , [36] . Due to the need for new NO donors with better pharmacological properties, we recently synthesized and characterized 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP) [27] .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the search for new therapies which increase NO bioavailability in cardiovascular diseases (CVDs) has been the target of numerous studies. Of note, organic nitrates such as sodium nitroprusside and glyceryl trinitrate, which mimic the role of endogenous NO in biological systems, have been used in the treatment of several cardiovascular diseases; such as arterial hypertension and coronary artery disease [16] , [17] , [18] , [19] , [20] , [21] , [22] . Despite their beneficial effects in patients with cardiovascular disease, these drugs have several clinical limitations.…”

Section: Introductionmentioning

confidence: 99%

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The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

et al. 2018

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RationaleDevelopment and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance. In this study, we evaluated NO release capability and cardiovascular effects of the newly synthesized organic nitrate 1, 3-bis (hexyloxy) propan-2-yl nitrate (NDHP).MethodsA combination of in vitro and in vivo approaches was utilized to assess acute effects of NDHP on NO release, vascular reactivity and blood pressure. The therapeutic value of chronic NDHP treatment was assessed in an experimental model of angiotensin II-induced hypertension in combination with NOS inhibition.ResultsNDHP mediates NO formation in both cell-free system and small resistance arteries, a process which is catalyzed by xanthine oxidoreductase. NDHP-induced vasorelaxation is endothelium independent and mediated by NO release and modulation of potassium channels. Reduction of blood pressure following acute intravenous infusion of NDHP was more pronounced in hypertensive rats (two-kidney-one-clip model) than in normotensive sham-operated rats. Toxicological tests did not reveal any harmful effects following treatment with high doses of NDHP. Finally, chronic treatment with NDHP significantly attenuated the development of hypertension and endothelial dysfunction in rats with chronic NOS inhibition and angiotensin II infusion.ConclusionAcute treatment with the novel organic nitrate NDHP increases NO formation, which is associated with vasorelaxation and a significant reduction of blood pressure in hypertensive animals. Chronic NDHP treatment attenuates the progression of hypertension and endothelial dysfunction, suggesting a potential for therapeutic applications in cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

et al. 2018

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“…We also observed a slight increase in HR. The tachycardic response produced by nitroglycerin is the most likely baroreflex-mediated [39]. Perhaps in our method, the baroreceptor reflex was inhibited by the pentobarbital used to anesthetize rats [32].…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Cardiorespiratory Parameters in Rats—Validation Based on Pharmacological Stimulation

et al. 2021

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The methods used in preclinical studies should minimize the suffering and the number of animals but still provide precise and consistent results enabling the introduction of drug candidates into the phase of clinical trials. Thus, we aimed to develop a method allowing us to perform preliminary safety and toxicity studies of candidates for human medicines, while reducing the number of animals. We have devised a method based on a combination of two devices: Plugsys (Transonics System Inc., Ithaca, NY, USA) and PhysioSuite (Kent Scientific Corporation, Torrington, CT, USA), which allow simultaneous registration of nine circulatory and respiratory parameters, and body temperature. Vehicle and adrenaline, or nitroglycerin, as reference substances were administered into the right femoral vein of Wistar rats. Physiological conditions were registered over 60 min after drug administration by measuring systolic, diastolic and mean blood pressure, heart rate (HR), blood perfusion of paw vessels, blood oxygen saturation, respiratory rate, average and peak exhaled CO2, and body temperature. Blood pressure was measured by cannula placed in the left common carotid artery and connected to the pressure transducer (Plugsys). The other parameters were measured by the PhysioSuite. Adrenaline-induced immediate dose-related hypertension and nitroglycerin hypotension were correlated with the change in blood perfusion. They both increased HR. Adrenaline decreased blood oxygen saturation and slightly affected respiratory parameters, while nitroglycerin caused a progressive increase in respiratory rate and a decrease in the peak of exhaled CO2. Our method may become an inseparable part of the preliminary safety and toxicity studies of tested drugs, while being an important step towards improving animal welfare.

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“…New chemical classes of NO donors have now been synthesized and may have potential for the treatment of CVDs. Our research group and others have studied some new NO donors which induced hypotension in normotensive rats such as (Z)-ethyl 12-nitrooxyoctadec-9-enoate (NCOE) [126] and cis-[Ru(bpy) 2 (py)(NO 2 )](PF 6 ) (RuBPY) [125] as well as in hypertensive animals, for instance 2-nitrate-1,3-dibuthoxypropan (NDBP) [228][229][230], the nitrosyl-ruthenium complex [Ru(terpy)(bdq)NO + ]3 + (TERPY) [231][232][233][234], the cyclohexane nitrate (HEX) [235], and the organic nitrate 1,3-bis (hexyloxy) propan-2-yl nitrate (NDHP) [236] (Table 1).…”

Section: Clinical Use and Limitations Of Nitric Oxide Donorsmentioning

confidence: 99%

Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors

Silva

Nascimento

et al. 2021

Biology

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Cardiovascular diseases include all types of disorders related to the heart or blood vessels. High blood pressure is an important risk factor for cardiac complications and pathological disorders. An increase in circulating angiotensin-II is a potent stimulus for the expression of reactive oxygen species and pro-inflammatory cytokines that activate oxidative stress, perpetuating a deleterious effect in hypertension. Studies demonstrate the capacity of NO to prevent platelet or leukocyte activation and adhesion and inhibition of proliferation, as well as to modulate inflammatory or anti-inflammatory reactions and migration of vascular smooth muscle cells. However, in conditions of low availability of NO, such as during hypertension, these processes are impaired. Currently, there is great interest in the development of compounds capable of releasing NO in a modulated and stable way. Accordingly, compounds containing metal ions coupled to NO are being investigated and are widely recognized as having great relevance in the treatment of different diseases. Therefore, the exogenous administration of NO is an attractive and pharmacological alternative in the study and treatment of hypertension. The present review summarizes the role of nitric oxide in hypertension, focusing on the role of new NO donors, particularly the metal-based drugs and their protagonist activity in vascular function.

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Cardiorespiratory effects induced by 2-nitrate-1,3-dibuthoxypropan are reduced by nitric oxide scavenger in rats

Cited by 8 publications

References 39 publications

The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

The novel organic mononitrate NDHP attenuates hypertension and endothelial dysfunction in hypertensive rats

Monitoring of Cardiorespiratory Parameters in Rats—Validation Based on Pharmacological Stimulation

Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors

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