You are on page 1of 3

Vasopressin

Also known as Arginine vasopressin(AVP) or Anti Diuretic hormone(ADH). It is secreted by posterior lobe of pituitary. Called vasopressin because it can constrict arterioles. Both the posterior lobe hormones ie AVP and Oxytocin are Nona-peptides ie have Nine Aminoacid sequence. The hormone is secreted in the Supraoptic and Paraventricular nuclei of Hypothalamus and transported down the axons of these neurons to their endings in the posterior lobe of pituitary. Secreted as precursor molecule, Prepropressophysin (in the ribosome of the neuron) processed in the Endoplasmic reticulum packaged into secretory granules called Herring Bodies, in the golgi apparatus granules are carried by axonic flow to the nerve endings in the posterior pituitary. Neurons generate action potential action potential reaching the terminal end Ca + + dependent exocytosis.

AVP and Oxytocin are also secreted in:

Gonads Adrenal cortex Thymus (only oxytocin)

AVP Receptors

V

1A :

V 1B :

Vasopressin receptors are of 3 types:

Act through phophotidyl inositol pathway ↑Ca ++ level It is found in Liver and Brain. Causes Glycogenolysis and is neurotransmitter in CNS Also act through phophotidyl inositol pathway ↑Ca ++ level

Found in Anterior Pituitary. Cause increased ACTH secretion. V 2 : Act through G s mediated cGMP pathway. Found in Kidney. Responsible for water absorption.

AVP acts on the Principal cells of the collecting duct. The action of AVP is mediated through V 2 receptors. It involves insertion of protein-water channel (Aquaporin 2) in the luminal surface of the principal cell of collecting duct.

In a typical 70-kg adult, the kidney filters about 180 L /d of plasma. Of this, approximately 144 L (80%) is reabsorbed isosmotically in the proximal tubule and another 8 L (4 to 5%) is reabsorbed without solute in the descending limb of Henle's loop. The remainder is diluted to an osmolality of about 60 mmol/kg by selective reabsorption of sodium and chloride in the ascending limb. In the absence of AVP, the urine issuing from the loop passes largely unmodified through the distal tubules and collecting ducts, resulting in a maximum water diuresis. In the presence of AVP, solute-free water is reabsorbed osmotically through the principal cells of the collecting ducts, resulting in the excretion of a much smaller volume of concentrated urine.

Mechanism of Action:

This antidiuretic effect is mediated via a G protein-coupled V 2 receptor that

increases intracellular cyclic AMP, thereby inducing translocation of aquaporin 2 (AQP2) water channels into the apical membrane. The resultant increase in permeability permits an influx of water that diffuses out of the cell through AQP3 and AQP4 water channels on the basal-lateral surface. The net rate of flux across the cell is determined by

the number of AQP2 water channels in the apical membrane and the strength of the osmotic gradient between tubular fluid and the renal medulla. Tight junctions on the lateral surface of the cells serve to prevent unregulated water flow.

o

o

Figure 1: Action of AVH

Mechanism of Action: This antidiuretic effect is mediated via a G protein-coupled V receptor that increases

Aquaporins are water channels. There are 5 types:

Aquaporin 1, 2 & 3 Aquaporin 4 Aquaporin 5

found in Kidney found in Brain found in salivary gland, lacrimal gland and respiratory tract

It is the Aquaporin 2 which is responsible for AVH mediated water absorption.

Control of AVH secretion

The secretion of AVP is regulated primarily by the "effective" osmotic pressure of body fluids. [ Normal Osmotic pressure is 280-296 mosm/kg H 2 O]

This control is mediated by specialized cells, known as osmoreceptors , located in the anteromedial hypothalamus near the supraoptic nucleus. They have inhibitory as well as stimulatory components that regulate AVP secretion around a specific set point. Thus, when plasma osmolality/sodium are depressed to a certain minimum or threshold level of ~280 mosmol/kg or 135 meq/L, respectively, plasma AVP is suppressed to low or undetectable levels and a water diuresis ensues. Conversely, when plasma osmolality/sodium rise above this "threshold," plasma AVP rises steeply in direct proportion, reaching a concentration sufficient to produce a maximum antidiuresis when plasma osmolality/sodium reach ~295 mosmol/kg and 143 meq/L. AVP secretion can also be influenced by acute changes in blood volume or pressure This baroregulation is mediated largely by neuronal afferents that originate in pressure receptors of the cardiac atria, aorta, and carotid arteries; project via the vagus and glossopharyngeal nerves to the nucleus tractus solitarius of the brain stem; and then ascend to the paraventricular and supraoptic nucleii of the hypothalmus. These pathways regulate AVP release by maintaining a tonic inhibitory tone that decreases when blood volume or pressure falls by >10 to 20%. AVP can also directly constrict arterioles hence called vasopressin. This baroregulatory system is probably of minor importance in the physiology of AVP secretion because the hemodynamic changes required to affect it are larger than those usually occurring in the course of normal activities. AVP secretion can also be stimulated by a variety of other nonosmotic variables including nausea, acute hypoglycemia, glucocorticoid deficiency, smoking, and, possibly, hyperangiotensinemia. The emetic stimuli are extremely potent since they typically elicit immediate, 50- to 100-fold increases in plasma AVP, even when the nausea is transient and unassociated with vomiting. They act via the emetic center in the medulla and can be completely blocked by treatment with antiemetics such as fluphenazine.

Summary of Control of AVH secretion

Increased AVP secretion

Decreased AVP secretion

↑Osmotic pressure

↓ Osmotic pressure

↓ ECF

↑ ECF

Emotion, Stress

Alcohol

Nausea, Vomiting

Standing

Angiotensin II

Diabetes Insipidus

Caused by decreased secretion or action of AVP. Characterised by abnormally large vol of dilute urine. 24 hr Urine vol > 50ml/Kg wt and osmolarity <300 mosm/L Treatment: DDAVP (Desmopressin) – is a synthetic AVP. Acts on V 2 receptor.