A5037651637- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Receptor Mechanisms and Signaling
- Heart Rate Variability and Autonomic Control
- Eicosanoids and Hypertension Pharmacology
- Phytochemicals and Antioxidant Activities
- Traditional Chinese Medicine Analysis
- Neuropeptides and Animal Physiology
- Antioxidant Activity and Oxidative Stress
- Cardiovascular Function and Risk Factors
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- S100 Proteins and Annexins
- Biochemical effects in animals
- Neurological Disease Mechanisms and Treatments
- Cardiac Imaging and Diagnostics
- Renin-Angiotensin System Studies
- Electron Spin Resonance Studies
- Neuroscience of respiration and sleep
- Diabetes Treatment and Management
- Free Radicals and Antioxidants
- Phytoestrogen effects and research
- Advanced Glycation End Products research
- Cardiac Arrest and Resuscitation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac electrophysiology and arrhythmias
Monash University
2006-2024
Baker Heart and Diabetes Institute
2019-2021
RMIT University
2010-2019
The University of Melbourne
2001-2012
MIT University
2010-2012
In-Q-Tel
2010
RMIT Europe
2010
Florey Institute of Neuroscience and Mental Health
2003-2007
Khon Kaen University
2000
Austin Hospital
1982-1992
The glucagon-like peptide-1 (GLP-1) receptor is a key regulator of insulin secretion and major therapeutic target for treatment diabetes. However, GLP-1 function complex, with multiple endogenous peptides that can interact the receptor, including full-length (1–37) truncated (7–37) forms each exist in an amidated form related peptide oxyntomodulin. We have investigated two allosteric modulators, Novo Nordisk compound 2 (6,7-dichloro2-methylsulfonyl-3-<i>tert</i>-butylaminoquinoxaline)...
The mechanism of the relaxant action and structure-activity relation flavonols (fisetin, quercetin, 3,3′, 4′-trihydroxyflavone) flavones (apigenin, chrysin, luteolin) were examined in rat isolated thoracic aorta. control responses to compared with observed after removal endothelium or presence L-type Ca2+ channel blocker, nifedipine (10−7M). effects flavonoids on contraction caused by influx extracellular agonist-induced release intracellular also investigated. exhibited...
BACKGROUND AND PURPOSE To investigate whether diabetes affects either or both nitric oxide (NO)‐mediated and endothelium‐derived hyperpolarizing factor (EDHF)‐type relaxation in endothelium‐dependent of mesenteric arteries from streptozotocin‐induced diabetic rats. EXPERIMENTAL APPROACH Wire myography was employed to examine endothelial function arteries. Superoxide levels were measured by L‐012 lucigenin‐enhanced chemiluminescence. Western blotting used quantify protein expression levels....
Abstract: We investigated the structure-activity relationships regarding vascular and antioxidant activity of a range synthetic flavonols flavones with 3 or fewer hydroxyl (OH) methoxyl substitutions. The relaxant responses ability flavones/flavonols to inhibit phenylephrine (PE)- Ca 2+ -induced contraction was determined in rat isolated thoracic aorta. these compounds reduce level superoxide preserve endothelium-dependent relaxation presence oxidative stress also examined. Four impaired PE...
3′,4′-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that can reduce injury after myocardial ischemia and reperfusion thus promising small molecule for the treatment of cardiovascular disease. Like all vasoactive flavonols reported to date, DiOHF both relaxant antioxidant, hindering investigation relative contribution each activity prevention injury. This study investigates structure–activity relationships variations at 3′ 4′ positions B ring vasorelaxant antioxidant activities....
Reactive oxygen species (ROS) such as superoxide have been linked to the hypertrophic response of heart stimuli including angiotensin II (AngII), mechanical stretch, and pressure overload. We previously demonstrated that cGMP protein kinase G mediate antihypertrophic actions natriuretic peptides in rat cardiomyocytes isolated whole hearts. The impact on cardiac ROS generation, however, has not investigated. tested hypothesis reduced accumulation contributes action atrial peptide...
The glucagon-like peptide 1 receptor (GLP-1R) is a promising target for the treatment of type II diabetes mellitus because its role in metabolic homeostasis. In recent years, difficulties with therapies have driven search small-molecule compounds to modulate activity this receptor. We recently identified quercetin, naturally occurring flavonoid, as probe-dependent, pathway-selective allosteric modulator GLP-1R-mediated signaling. Using Chinese hamster ovary cells expressing human GLP-1R, we...
The objective was a comprehensive investigation of the mechanisms and sites resveratrol cardioprotection during following ischemia-reperfusion (I-R) injury, to determine whether direct preservation cardiomyocytes is an important site cardioprotection. We now provide first definitive evidence that specifically protects from I-R injury via combination suppression superoxide levels activation potassium channels. This protection apparent present for full duration insult or only on recovery. In...
3',4'-Dihydroxyflavonol (DiOHF) is an effective antioxidant that acutely preserves nitric oxide (NO) activity in the presence of elevated reactive oxygen species (ROS). We hypothesized DiOHF treatment (7 days, 1 mg/kg per day s.c.) would improve relaxation mesenteric arteries from diabetic rats where endothelial dysfunction associated with oxidant stress.In there was increase ROS, measured by L-012 and 2',7'-dichlorodihydrofluorescein diacetate fluorescence. NADPH oxidase-derived superoxide...
Abstract Aging is associated with chronic, low‐level inflammation which may contribute to cardiovascular pathologies such as hypertension and atherosclerosis. This chronic be opposed by endogenous mechanisms limit inflammation, for example, the actions of annexin A1 (ANXA1), an glucocorticoid‐regulated protein that has anti‐inflammatory pro‐resolving activity. We hypothesized mediator ANXA1 protects against age‐induced changes in blood pressure (BP), structure function, cardiac senescence....
Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver hypertension-induced end-organ damage. We have previously reported that biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal first compelling evidence therapeutic potential this novel agonist longer-term, sustained insult, i.e. The parallels between murine and human hypertensive proteome were also investigated.
The use of estrogen for protection against vascular dysfunction is limited due to its effects on the reproductive system, particularly in males. We postulated that daidzein, an isoflavone with estrogen-like systemic vasculature but not might enhance nitric oxide (NO)-mediated cerebral vasodilatation. Male rats were administered vehicle, 17beta-estradiol (0.1 mg/kg s.c.), or daidzein (0.2 s.c.) daily 7 days. Basal and acetylcholine-stimulated NO release was assessed vitro via carotid arterial...
Isoflavones, such as daidzein, are proposed to possess vasculoprotective properties, perhaps through a mechanism similar estrogen. Our experiments aimed test the hypothesis that daidzein and 17 beta-estradiol enhance endothelium-dependent relaxation an increase in NO synthesis due activity or expression of endothelial nitric oxide synthase (eNOS). Male rats were treated with (0.2 mg/kg per day sc), (0.1 vehicle for 7 days reactivity isolated aortic rings was then determined. ACh-induced...