Vasopressin is a hormone that plays a role in maintaining osmotic balance in the body. This hormone is also called arginine vasopressin (AVP) and antidiuretic hormone. It has vasoconstrictor properties. Because of its vasoconstrictive property, its use is being researched in managing vasodilatory shock.
What Is Vasopressin?
Vasopressin is a nine-amino acid peptide hormone that is produced in the hypothalamus. This peptide is called the pre-pro hormone. These peptides travel through the axons of neurons to the posterior pituitary gland. Vasopressin is stored in the posterior pituitary gland, and only 10-20% of it is released on stimulation of the blood circulation.
Vasopressin secretion is regulated by plasma osmolality, blood volume, and blood pressure. Plasma osmolality is very important for maintaining vasopressin levels. Whenever there is a 2% decrease in whole-body water, the concentration of vasopressin hormones can be doubled. Increased plasma osmolality increases vasopressin levels in plasma as osmoreceptors in the hypothalamus respond to this change.
Hypovolemia and hypotension caused by vasopressin can induce stimulation of atrial volume receptors and carotid baroceptors. This again results in the secretion of vasopressin.
Vasopressin secretion is more sensitive to slight changes in osmolality than hypotension-related secretion. Due to changes in hypotension, vasopressin secretion requires enormous pressure and volume variation. Vasopressin is released due to pain, nausea, and hypoxia. Vasopressin release is reduced by the heart due to elevated cardiac wall stress. It is also released by the adrenal gland in response to increased catecholamine secretion.
Vasopressin has a plasma half-life of 5-15 minutes. Its clearance is dependent on renal and liver vasopressinases. It binds to three receptors in the periphery. These receptors are V1a, V1b, and V2.
V1a - These are situated on vascular smooth muscle cells; whenever these get activated, smooth muscle cells are contracted. Activation of V1a receptors causes platelet aggregation.
V1b - These are situated in the anterior pituitary and pancreas. Vasopressin is responsible for the increased secretion of cortisol and insulin.
V2 - These receptors are situated on the surface of the renal tubular cells, especially on the collecting ducts. When vasopressin binds to these receptors, there is recruitment of aquaporin 2. This results in the reabsorption of water by the epithelial membrane. Extra-renal V2 receptors help in the release of coagulating factors. Synthetic analogs have higher vascular specificity when compared to natural AVP when tested in pre-clinical shock models.
What Are the Mechanisms of Action of Vasopressin on Vascular Smooth Muscles?
The action of vasopressin in vascular smooth muscle contraction pathways: Mechanisms by which vasopressin restores vascular tone in vasoplegic (catecholamine-resistant) shock state include
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By activating V1a receptors.
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Modulating ATP-sensitive K+channels (KATP)
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Modulating nitric oxide (NO)
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Potentiating adrenergic and other vasoconstrictor agents.
All cells in muscles use calcium for the contraction action as a signal. Many neurotransmitters and hormones regulate the action of smooth muscle cells. These interact with signal pathways and affect contractility by affecting the cell's calcium levels or the contractile apparatus's response to calcium.
When a high calcium concentration is present in the cytosol, it forms a complex with calmodulin. This complex activates myosin ATPase through actin. Myosin ATPase and the cycling of myosin cross-bridges with actin filaments help contract muscles. Vasodilatation occurs when kinase interacts with myosin phosphatase. This dephosphorylates myosin and stops muscle contraction.
Vasopressin, norepinephrine, and angiotensin II act on receptors present in the smooth muscles, and these receptors bind with vasopressin-like G proteins and affect vasoconstriction.
Vasopressin binds to V1a receptors that are present in the smooth muscles. It acts through the Gq/11 pathway, stimulates phospholipase C, and produces intracellular messengers called inositol triphosphate (IP3) and diacylglycerol. These messengers activate protein kinase C and increase free calcium levels in the cell. This, in turn, helps in the vasoconstriction of smooth muscles.
Vasodilators like atrial natriuretic peptide (ANP) and NO activate the cGMP-dependent kinase. This cGMP-dependent kinase interacts with myosin phosphatase and dephosphorylates myosin. This action helps prevent the contraction of smooth muscles. This opposing action is important for the functioning of vascular smooth muscles. This type of signaling is important for vascular homeostasis.
The resting membrane potential of vascular smooth muscle is -30mV to -60mV. When there is more positive potential (depolarization), it opens the voltage-gated calcium channels and increases the calcium concentration in the cell. This brings about the vasoconstriction action in the vascular smooth muscles. In opposition to this action, when hyperpolarization occurs, it closes all the channels and decreases the cytosolic calcium concentration in the cells. This brings about vasodilation.
The membrane potential is controlled by many ion transporters and channels. K+ channels are essential among ion transporters and channels. Among the K+ channels, KATP channels are important and play a role in vasodilatory shock. Activation of KATP channels causes hypotension and vasodilation in vasodilatory shock. Vasopressin helps restore vascular tone in vasoplegic shock by closing KATP channels.
The NO is responsible for hypotension and resistance to vasopressor drugs in vasodilatory shock. Vasopressin restores vascular tone by blunting the cGMP that is induced by NO and ANP. Vasopressin also decreases the synthesis of nitric oxide synthase (NOS), which is stimulated by lipopolysaccharide via V1a.
Vasopressors help increase the vasoconstriction action of many agents like angiotensin II and norepinephrine. This mechanism is mostly due to the coupling of vasopressin with receptors present in the vascular smooth muscles.
Vasopressin is also involved in bringing about vasodilatation. But this occurs in particular vascular beds. The vasodilatation action of vasopressin is due to the activation of endothelial oxytocin receptors (OTRs). These receptors, in turn, trigger and activate endothelial isoforms of NOS.
The action of vasoconstriction or vasodilatation by vasopressin depends on the vascular bed, receptors, and dosage of vasopressin.
What Are the Effects of Vasopressin on the Heart?
The action of vasopressin on the heart is very complex. Depending on the dosage, it may cause coronary vasoconstriction or vasodilatation. It may cause positive or negative ionotropic effects. Apart from these actions, Vasopressin has mitogenic and metabolic effects on the heart.
Conclusion:
Vasopressin is a hormone and a neurotransmitter that has a role in the control of vascular tone and affects the myocardium. Hence, it can be used as a treatment for many conditions related to coronary heart diseases, like shock. Vasopressin can restore vascular tone and be used as a first-line therapy for vasodilatory shock. Hence, it is important to know about vasopressin, its mechanisms of action in restoring vascular tone, and its effects on the heart. Knowing this helps one seek help from a healthcare professional early. Early diagnosis leads to effective treatment. This, in turn, helps achieve a good quality of life.
