Endothelium-derived relaxing factor

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Nitric Oxide (NO), the principal EDRF Nitric-oxide-2D.png
Nitric Oxide (NO), the principal EDRF

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. [1] 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. [2] [3]

Contents

Physiological Functions and production

Anatomical cross section of an artery: the "intima" is composed of endothelial cells Microscopic anatomy of an artery en.svg
Anatomical cross section of an artery: the "intima" is composed of endothelial cells

EDRF serves various functions, of which the most common and topical are vasodilation and the prevention of platelet adhesion. EDRF also plays a role in the production of cyclic GMP.[ citation needed ]

EDRF is produced from L-arginine by an enzyme (endothelial nitric oxide synthase) that is dependent on calcium-calmodulin and NADPH - this occurs in the cardiac endothelium.[ citation needed ]

EDRF then diffuses to the smooth muscle in vascular tissue (vessels may be large or small), here it enacts endogenous vasodilation. Moreover, it serves the function of preventing sympathetic vasoconstriction - when the sympathetic nervous system, reacting to a situation perceived as dangerous, attempts to raise blood pressure through vasoconstriction.[ citation needed ]

The NO compound is also capable of reducing clotting in the blood stream due to its ability to prevent platelet adhesion and aggregation. [4]

Atherosclerosis and hypertension are grave contributors in the group of pathological conditions under the umbrella of Cardiovascular disease. Among these conditions is also the disfunction of the endothelium, which given its properties of vasodilation when functional, can cause excessive vasoconstriction, thus leading back to hypertension. Another effect of this particular disfunction may also be excessive platelet adhesion, signifying a significant increase in blood clots, thus the promotion of a prothrombotic state. [4]

Related Research Articles

<span class="mw-page-title-main">Blood vessel</span> Tubular structure of circulatory system

Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from the tissues. Blood vessels are needed to sustain life, because all of the body's tissues rely on their functionality.

<span class="mw-page-title-main">Nitric oxide</span> Colorless gas with the formula NO

Nitric oxide is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula. Nitric oxide is also a heteronuclear diatomic molecule, a class of molecules whose study spawned early modern theories of chemical bonding.

<span class="mw-page-title-main">Robert F. Furchgott</span> American biochemist (1916–2009)

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.

<span class="mw-page-title-main">Vasodilation</span> Widening of blood vessels

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. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.

<span class="mw-page-title-main">Arteriole</span> Small arteries in the microcirculation

An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.

In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel. It is the first stage of wound healing. Hemostasis involves three major steps:

<span class="mw-page-title-main">Endothelium</span> Layer of cells that lining inner surface of blood vessels

The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue.

Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create blood flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be called by the older term total peripheral resistance (TPR), while the resistance offered by the pulmonary circulation is known as the pulmonary vascular resistance (PVR). Systemic vascular resistance is used in calculations of blood pressure, blood flow, and cardiac function. Vasoconstriction increases SVR, whereas vasodilation decreases SVR.

<span class="mw-page-title-main">Endothelial dysfunction</span>

In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. The main cause of endothelial dysfunction is impaired bioavailability of nitric oxide,

Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.

<span class="mw-page-title-main">Endothelin</span>

Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases.

In blood vessels Endothelium-Derived Hyperpolarizing Factor or EDHF is proposed to be a substance and/or electrical signal that is generated or synthesized in and released from the endothelium; its action is to hyperpolarize vascular smooth muscle cells, causing these cells to relax, thus allowing the blood vessel to expand in diameter.

<span class="mw-page-title-main">Louis Ignarro</span> American pharmacologist

Louis Joseph Ignarro 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.

There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, which constricts the smooth muscles of the blood vessels, raising blood pressure, or relaxes the smooth muscles of the blood vessels, lowering blood pressure, among other functions.

<span class="mw-page-title-main">Endothelial NOS</span> Protein and coding gene in humans

Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.

Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke patients. It has been found to be effective for the treatment of pulmonary hypertension. It has been demonstrated that fasudil could improve memory in normal mice, identifying the drug as a possible treatment for age-related or neurodegenerative memory loss.

Biological functions of nitric oxide are roles that nitric oxide plays within biology.

<span class="mw-page-title-main">Methylarginine</span> Chemical compound

N-Methylarginine is an inhibitor of nitric oxide synthase. Chemically, it is a methyl derivative of the amino acid arginine. It is used as a biochemical tool in the study of physiological role of nitric oxide.

<span class="mw-page-title-main">Protein detoxification</span>

Protein detoxification is the process by which proteins containing methylated arginine are broken down and removed from the body.

Thromboregulation is the series of mechanisms in how a primary clot is regulated. These mechanisms include, competitive inhibition or negative feedback. It includes primary hemostasis, which is the process of how blood platelets adhere to the endothelium of an injured blood vessel. Platelet aggregation is fundamental to repair vascular damage and the initiation of the blood thrombus formation. The elimination of clots is also part of thromboregulation. Failure in platelet clot regulation may cause hemorrhage or thrombosis. Substances called thromboregulators control every part of these events.

References

  1. "Endothelium Derived Relaxing Factor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-01-21.
  2. Bauer, Viktor; Sotníková, Ružena (29 December 2010). "Nitric oxide--the endothelium-derived relaxing factor and its role in endothelial functions". General Physiology and Biophysics. 29 (4): 319–340. doi: 10.4149/gpb_2010_04_319 . ISSN   0231-5882. PMID   21156995.
  3. Francis, S. H.; Busch, J. L.; Corbin, J. D. (2010-09-01). "cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action". Pharmacological Reviews. 62 (3): 525–563. doi:10.1124/pr.110.002907. ISSN   0031-6997. PMC   2964902 . PMID   20716671.
  4. 1 2 Pirahanchi, Yasaman; Marsidi, Jennifer L.; Brown, Kristen N. (2022), "Physiology, Endothelial Derived Relaxation Factor", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   30725695 , retrieved 2023-01-21