Control of tissue blood flow by endothelial-derived relaxation or contraction factors
The most important of the endothelial vasodilators is NO, a lipophilic gas released from endothelial cells in response to a variety of chemical and physical stimuli.
Endothelial cells that line the blood vessels synthesize several substances that, when released, can affect the contraction or relaxation of the vessel wall. The role of physiologists is only to understand and apply them clinically in most cases but not to develop them.
Nitro oxide - a vasoconstrictor released from healthy endothelial cells
The most important of the endothelial vasodilators is NO, a lipophilic gas released from endothelial cells in response to a variety of chemical and physical stimuli. The NO synthase enzyme synthesizes NO from arginine and oxygen and by reducing inorganic nitrates. After diffusing out of the endothelial cells, NO has a half-life of about 6 minutes and is active mainly in the local tissue where it is released. NO activates Guanyl cyclase in skeletal muscle cells to convert cGTP to cGMP and activates PKG, PKG has a vasodilating effect.
Figure. Nitric oxide synthase (eNOS) - an enzyme in endothelial cells that synthesizes NO from arginine and oxygen. NO activates guanyl cyclase in vascular smooth muscle cells, leading to the conversion of cGTP to cGMP, which ultimately helps to relax blood vessels.
Blood flow through arteries and arterioles causes “shear stress” on endothelial cells due to the viscosity of the blood against the vessel wall. The pressure causes the endothelial cells to distort in the direction of blood flow and causes a significant increase in NO released, NO released to relax the vessel wall, which is advantageous, because the metabolic topical to control blood flow mainly causes constriction of small arteries and arterioles in each tissue. As blood flow through the microvascular portion of the circulation increases, this phenomenon has a secondary role in encouraging the release of NO from the great vessels as a result of increased blood flow and "shear stress" on these vessels. this blood vessel. The released NO increases the diameter of the larger upstream blood vessel, whenever the microvasculature increases downstream. If no response,
The synthesis and release of NO from endothelial cells are also encouraged by some vasoconstrictors such as angiotensin 2- which binds to specific receptors on endothelial cells. The increased release of NO will protect against excessive vasoconstriction.
When endothelial cells are destroyed by chronic hypertension or atherosclerosis, damaged NO synthesis contributes to excessive vasoconstriction and worsens hypertension and the destruction of endothelial cells. tissue, which, if left untreated, can eventually cause vascular damage and destruction of vulnerable tissues such as the heart, kidneys, and brain.
Even before NO was examined, clinicians were already using nitro-glycerine, amyl nitrate, and nitrate derivatives to treat patients with angina, severe chest pain caused by myocardial ischemia. These drugs, when broken down, release NO and stimulate vasodilation throughout the body, including the coronary arteries.
Another important application of NO in physiology and pharmacology is the development and clinical use of drugs that inhibit cGMP-specific phosphodiesterase (PDE-5), an enzyme that degrades cGMP. By blocking cGMP degradation, PDE-5 inhibitors prolong NO activity with vasoconstriction. The first clinical application of PDE-5 inhibitors was in the treatment of erectile dysfunction. Penile erection is caused by a parasympathetic nerve impulse that travels through the pelvic nerve to the penis, where the neurotransmitters acetylcholine and NO are released. By blocking the breakdown of NO, PDE-5 inhibitors increase blood vessel dilation in the penis, supporting an erection.
Endothelin-A's powerful vasoconstriction released from the destroyed inner membrane
Endothelial cells also release vasoconstrictor substances. One of the most important is the large endothelin-peptide containing 27 amino acids, which in very small amounts (nanograms) can cause strong vasoconstriction. This substance is present in the endothelial cells of most blood vessels but is most elevated when the blood vessel is injured. This abnormal stimulation is detrimental to the endothelium, which is caused by compression of tissues or injection of chemicals that damage blood vessels. After extensive destruction of blood vessels, local release of endothelin and subsequent vasoconstriction helps to prevent extensive bleeding from arteries up to 5 millimetres in diameter that can be caused by lesion compression. .
That increased endothelin release is also expected to contribute to vasoconstriction when the endothelin receptor is also used to lower blood pressure in patients with systemic arterial hypertension.