A5073267685- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Renin-Angiotensin System Studies
- Cardiovascular Health and Disease Prevention
- Heart Rate Variability and Autonomic Control
- Blood Pressure and Hypertension Studies
- Neuroscience of respiration and sleep
- Sports injuries and prevention
- Tendon Structure and Treatment
- Cardiovascular Issues in Pregnancy
- Receptor Mechanisms and Signaling
- Pregnancy and preeclampsia studies
- Renal function and acid-base balance
- Shoulder Injury and Treatment
- Pulmonary Hypertension Research and Treatments
- Neuropeptides and Animal Physiology
- Sports Performance and Training
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Cancer-related gene regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory mediators and NSAID effects
- Cardiac Ischemia and Reperfusion
- Pharmaceutical Economics and Policy
- Birth, Development, and Health
La Trobe University
2024-2025
Monash University
2019-2025
Monash Health
2025
The University of Melbourne
2021-2024
Natural History Museum
2023
Museum of London
2023
Government of the United Kingdom
2023
Peninsula Health
2019-2021
University of California, Davis
2020
Department of Health and Social Care
2020
There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis acute infection and vaccination increase short-term risk of vascular events.
Systemic inflammation may impair vascular function, and epidemiologic data suggest a possible link between periodontitis cardiovascular disease.
Background —We tested the hypothesis that endothelial dysfunction underlies association between an acute inflammatory episode and transiently increased risk of a cardiovascular event by examining effects experimental stimulus on endothelium-dependent vasodilation. Methods Results — Salmonella typhi vaccine was used to generate systemic response in healthy volunteers. In 12 subjects, dilatation brachial artery flow sublingual nitroglycerin (NTG) recorded (conduit vessel response), 6 venous...
Plasma levels of an endogenous nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA), are elevated in chronic renal failure, hypertension, and heart failure. In patients with plasma ADMA independent correlate left ventricular ejection fraction. However, the cardiovascular effects a systemic increase humans not known.In randomized, double-blind, placebo-controlled study 12 healthy male volunteers, we compared intravenous low-dose placebo on rate, blood pressure, cardiac...
Patients with insulin-dependent diabetes mellitus have an increased mortality and morbidity due to vascular complications. Nitric oxide from the endothelium contributes control of normal tone, endothelial dysfunction has been implicated in pathogenesis diabetic disease. In this study we examined basal stimulated nitric oxide-mediated vasodilatation diabetics age- sex-matched healthy controls. Drugs were infused locally into brachial artery forearm blood flow measured using venous occlusion...
Summary: Nitric oxide (NO) is a widespread biological mediator with myriad functions. We have demonstrated that methylated arginines capable of inhibiting NO synthesis circulate in the plasma healthy volunteers and are excreted unchanged urine. Up to 10 mg asymmetric dimethylarginine urine every day, this compound inhibits vitro vivo, animals humans. This finding raises possibility these compounds may act as endogenous regulators L-arginine:NO pathway health disease.
Methylarginines inhibit nitric oxide synthases (NOS). Cellular concentrations of methylarginines are determined in part by the activity dimethylarginine dimethylaminohydrolase (DDAH; EC 3.5.3. 18). We have cloned human DDAH and identified expressed a second novel isoform (DDAH I II respectively). predominates tissues that express neuronal NOS. expressing endothelial These results strengthen hypothesis methylarginine concentration is actively regulated identify molecular targets for tissue...
Dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes the endogenous nitric oxide synthase inhibitors N G ‐monomethyl‐L‐arginine and , ‐dimethy‐L‐arginine to citrulline, was identified by Western blotting in rat human tissue homogenates. S‐2‐amino‐4(3‐methylguanidino)butanoic acid (4124W) inhibited metabolism of [ 14 C]‐N C]‐citrulline liver homogenates (IC 50 416 ± 66μ m ; n = 9), cultured endothelial cells 250 34 μ 9)and isolated purified dimethylarginine...
Background Endothelial dysfunction occurs in many diseases associated with increased cardiovascular risk. We examined the effects of pro-inflammatory cytokines on endothelial function. Methods and Results Subjects lay one hand placed an angled support. The diameter a vein was recorded by measuring linear displacement probe skin overlying when pressure congesting cuff around upper arm deflated from 40 to 0 mm Hg. A length isolated two wedges. TNF-α (1 ng), IL-1β or IL-6 (100 pg) were...
Venous occlusion plethysmography has been widely used to study forearm blood flow. The principle of the technique is straightforward: rate swelling during venous return assess arterial inflow. Provided that perfusion pressure (arterial pressure) remains constant, changes in flow reflect smooth muscle tone small arteries and arterioles. Local infusion into brachial artery allows assessment direct effect drugs on vascular probe roles endogenous mediators. at its most powerful when...
Abstract —Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intact endothelium, although the mechanisms are not fully understood. Using high-resolution ultrasound, we examined role endothelial mediators in radial artery response to transient (short period reactive hyperemia) and sustained (prolonged hyperemia, hand warming, or incremental infusion acetylcholine into distal artery) hyperemia. After short episodes FMD was abolished by local nitric oxide synthesis inhibitor...
NO is a major regulator of cardiovascular physiology that reduces vascular and cardiac contractility. Accumulating evidence indicates endogenous inhibitors may regulate NOS. The NOS asymmetric dimethylarginine (ADMA) N-monomethylarginine are metabolized by the enzyme dimethylaminohydrolase (DDAH). This study was designed to determine if increased expression DDAH could reduce tissue plasma levels thereby increase synthesis.We used gene transfer transgenic approaches overexpress human I in...
Background —Endothelial dysfunction leading to neutrophil infiltration of tissues has been implicated in tissue injury caused by ischemia-reperfusion (IR). Tissue during IR can be reduced prior ischemic preconditioning (IPC). In humans, it is unclear whether endothelial occurs or IPC offers protection against and inflammatory cell activation. We studied the effects experimental on function human forearm vivo examined afforded IPC. Method Results —The was made for 20 minutes inflating a blood...