The HNO donor Angeli’s salt offers potential haemodynamic advantages over NO or dobutamine in ischaemia–reperfusion injury in the rat heart ex vivo

Chin, Kai Yee; Michel, Lisa; Qin, Cheng Xue; Cao, Nga; Woodman, Owen L.; Ritchie, Rebecca H.

doi:10.1016/j.phrs.2015.12.006

Cited by 18 publications

(11 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rat hearts were equilibrated for 20 min with steady-flow and hearts exhibiting poor function (e.g., heart rate <100 beats/min and LV+dP/dt < 1,500 mmHg/sec) during equilibration were excluded from the study (Chin et al, 2016). After equilibration, each heart was subjected to 20 min of global ischemia and 60 min of reperfusion (Whittington et al, 2013).…”

Section: Langendorff Perfusion and Ischemia-reperfusion Injury Ex Vivomentioning

confidence: 99%

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

et al. 2019

Self Cite

View full text Add to dashboard Cite

Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo. These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine.

show abstract

Section: Langendorff Perfusion and Ischemia-reperfusion Injury Ex Vivomentioning

confidence: 99%

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whilst the discussion so far has focused on circumventing NO• resistance in the vasculature and platelets, it is pertinent to note that the myocardium is also susceptible to NO• resistance, such that NO• can no longer enhance left ventricular (LV) relaxation (Qin et al, 2020). Thus, following ischemia-reperfusion (I-R) injury (Chin et al, 2016) or the induction of T1DM (Qin et al, 2020) in rats, the ability of the NO• donor, DEA/NO to enhance myocardial relaxation is impaired. Such an impairment in myocardial responsiveness to NO• (endogenous or exogenous) may facilitate LV dysfunction, LV hypertrophy and cardiac remodelling (Nightingale et al, 2011;Sverdlov et al, 2011).…”

Section: Nitroxyl-based Therapiesmentioning

confidence: 99%

“…On the contrary, nitroxyl (HNO) donors circumvent NO• resistance and thus promote vasodilation, while uniquely inducing positive inotropic and lusitropic responses that persist in conditions of oxidative stress (e.g. heart failure, diabetes) where responses to NO• are diminished (Paolocci et al, 2003;Chin et al, 2016;Tare et al, 2017;Qin et al, 2020). Although the aforementioned cardiovascular changes are associated with both T1DM and T2DM, due to the prevalence of the latter, this review will explore the major mechanisms that drive impairments in NO• signaling in T2DM, and highlight the therapeutic potential of HNO donors to circumvent this problem, in order to alleviate acute hemodynamic complications in T2DM.…”

Section: Introductionmentioning

confidence: 99%

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

et al. 2020

Self Cite

View full text Add to dashboard Cite

Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, termed NO• resistance, compromises the ability of traditional NO•-based therapeutics to improve hemodynamic status during diabetes-associated cardiovascular emergencies, such as acute myocardial infarction. Whilst a number of agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins and insulin) or circumvent (e.g. nitrite and sGC activators) NO• resistance, nitroxyl (HNO) donors offer a novel opportunity to circumvent NO• resistance in diabetes. With a suite of vasoprotective properties and an ability to enhance cardiac inotropic and lusitropic responses, coupled with preserved efficacy in the setting of oxidative stress, HNO donors have intact therapeutic potential in the face of diminished NO• signaling. This review explores the major mechanisms by which hyperglycemia-induced oxidative stress drives NO• resistance, and the therapeutic potential of HNO donors to circumvent this to treat cardiovascular complications in type 2 diabetes mellitus.

show abstract

“…hearts, and holds hemodynamic advantages over existing pharmacotherapy in acute heart failure (27). Mechanistically, HNO elicits both inotropy and lusitropy via interacting with specific thiol proteins involved in Ca 2+ release and uptake within the sarcoplasmic reticulum (SR) (50,52).…”

Section: Fig 6 Antioxidant Effects Of Gshmentioning

confidence: 99%

Nitroxyl as a Potential Theranostic in the Cancer Arena

Sun

Lee

Leng

et al. 2020

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: As one-electron reduced molecule of nitric oxide (NO), nitroxyl (HNO) has gained enormous attention because of its novel physiological or pharmacological properties, ranging from cardiovascular protective actions to antitumoricidal effects. Recent Advances: HNO is emerging as a new entity with therapeutic advantages over its redox sibling, NO. The interests in the chemical, pharmacological, and biological characteristics of HNO have broadened our current understanding of its role in physiology and pathophysiology. Critical Issues: In particular, the experimental evidence suggests the therapeutic potential of HNO in tumor pharmacology, such as neuroblastoma, gastrointestinal tumor, ovarian, lung, and breast cancers. Indeed, HNO donors have been demonstrated to attenuate tumor proliferation and angiogenesis. Future Directions: In this review, the generation and detection of HNO are outlined, and the roles of HNO in cancer progression are further discussed. We anticipate that the completion of this review might give novel insights into the roles of HNO in cancer pharmacology and open up a novel field of cancer therapy based on HNO. Antioxid. Redox Signal. 32, 331-349.

show abstract

The HNO donor Angeli’s salt offers potential haemodynamic advantages over NO or dobutamine in ischaemia–reperfusion injury in the rat heart ex vivo

Cited by 18 publications

References 36 publications

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

Nitroxyl as a Potential Theranostic in the Cancer Arena

Contact Info

Product

Resources

About