Robert Francis Furchgott was a Nobel Prize-winning American biochemist who contributed to the discovery of nitric oxide as a transient cellular signal in mammalian systems.
Vasodilation,also known as vasorelaxation,is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls,in particular in the large veins,large arteries,and smaller arterioles. The process is the opposite of vasoconstriction,which is the narrowing of blood vessels.
The Endothelium-derived relaxing factor (EDRF) is a strong vasodilator produced by cardiac endothelial cells in response to stress signals such as high levels of ADP accumulation or hypoxia. Robert F. Furchgott is widely recognised for this discovery,even going so far as to be a co-recipient of the 1998 Nobel Prize in Medicine with his colleagues Louis J. Ignarro and Ferid Murad. Nitric oxide (NO) is a key component in any EDRF as these compounds either include NO or are structurally in the form of NO.
Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone,insulin secretion,airway tone,and peristalsis,and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform,iNOS,involved in immune response,binds calmodulin at physiologically relevant concentrations,and produces NO as an immune defense mechanism,as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.
Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues,most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.
Sir Salvador Enrique Moncada Seidner,FRS,FRCP,FMedSci is a Honduran pharmacologist and professor. He is currently Research Domain Director for Cancer at the University of Manchester.
Louis JoséIgnarro is an American pharmacologist. For demonstrating the signaling properties of nitric oxide,he was co-recipient of the 1998 Nobel Prize in Physiology or Medicine with Robert F. Furchgott and Ferid Murad.
Denis Noble is a British physiologist and biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at the University of Oxford from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of systems biology and developed the first viable mathematical model of the working heart in 1960. Noble established The Third Way of Evolution (TWE) project with James A. Shapiro which predicts that the entire framework of the modern synthesis will be replaced.
The pacemaker current is an electric current in the heart that flows through the HCN channel or pacemaker channel. Such channels are important parts of the electrical conduction system of the heart and form a component of the natural pacemaker.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene.
Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels are integral membrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred to as pacemaker channels because they help to generate rhythmic activity within groups of heart and brain cells. HCN channels are activated by membrane hyperpolarization,are permeable to Na + and K +,and are constitutively open at voltages near the resting membrane potential. HCN channels are encoded by four genes and are widely expressed throughout the heart and the central nervous system.
Biological functions of nitric oxide are roles that nitric oxide plays within biology.
Purinergic signalling is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells,thereby regulating cellular functions.
George Edward Billman is an American physiologist and professor at Ohio State University. After receiving a Ph.D from the University of Kentucky in 1980,Billman began his professional career at the University of Oklahoma. In 1984,he joined the Ohio State staff,where he became an associate professor in 1990 and a full professor in 1996.
David Alfred Eisner,FRCP (Hon),FMedSci,is British Heart Foundation Professor of Cardiac Physiology at the University of Manchester and editor-in-chief of The Journal of General Physiology (JGP).
Sir Patrick John Thompson Vallance is a British physician,scientist,and clinical pharmacologist who has worked in both academia and industry. He served as the Chief Scientific Adviser to the Government of the United Kingdom from 2018 to 2023.
Jonathan Solomon Stamler is an English-born American physician and scientist. He is known for his discovery of protein S-nitrosylation,the addition of a nitric oxide (NO) group to cysteine residues in proteins,as a ubiquitous cellular signal to regulate enzymatic activity and other key protein functions in bacteria,plants and animals,and particularly in transporting NO on cysteines in hemoglobin as the third gas in the respiratory cycle.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases,such as glaucoma,asthma,urinary,gastrointestinal and cardiopulmonary disorders.
John Thompson Shepherd was a British-American cardiologist,medical researcher in cardiovascular physiology,and medical school dean. His research on the regulation of the cardiovascular system included "classic studies on reflex control of the circulation,haemodynamic responses to heat stress and exercise,and mechanisms of vasodilation."
Dario DiFrancesco is a Professor Emeritus (Physiology) at the University of Milano. In 1979,he and collaborators discovered the so-called "funny" current in cardiac pacemaker cells,a new mechanism involved in the generation of cardiac spontaneous activity and autonomic regulation of heart rate. That initiated a new field of research in the heart and brain,where hyperpolarization-activated,cyclic nucleotide-gated (HCN) channels,the molecular components of "funny" channels cloned in the late 90's,are today known to play fundamental roles in health and disease. Clinically relevant exploitation of the properties of "funny" channels has developed a channel blocker with specific heart rate-slowing action,ivabradine,marketed for the therapy of coronary artery disease,heart failure and the symptomatic treatment of chronic stable angina.
