1. Antidiuretic Hormone (ADH)
By Jill Ruiz Carreon

2. Also known as… Arginine vasopressin (AVP) Argipressin
“Pressor” effect is secondary significance
“Pressor” = rise in BP due to vasoconstriction

3. Antidiuretic Hormone 9 amino acids Produced in hypothalamus
Released from posterior pituitary (pars nervosa) to the blood
Stimulates water retention in the kidneys
Less water excreted in urine
Regulates and balances water in blood
 [H2O]   blood V and P

4. ADH & the CNS
Released into the brain by neurons of the hypothalamo-hypophyseal tract
Suprachaismatic nuclei (SCN)
Regulation of circadian rhythms
Circadian clock genes – transcribed into mRNA  proteins
Role in species-typical patterns of social behavior

5. ADH & the Cardiovascular System
Hypotension
Increases vasoconstriction  Arterial BP
Compensatory / Regulatory
However, also seen in patients with heart failure
Too many AVP receptors / AVP secretion
Sympathetic and renin-angiotensin system activation in heart failure override hypothalamic control of AVP release
May contribute to the increase in systemic vascular resistance as well as in renal retention of fluid
Minimal pressor effects in humans

6. ADH & the Kidneys Regulation of extracellular fluid
Conserve body water by reducing urine output
ADH binds to aquaporins in the plasma membranes of the collecting duct epithelial cells
Transports solute-free water through tubular cells
Back into blood
Decreases plasma osmolarity and increases urine osmolarity

7. ADH can be categorized as having these two primary action sites:
-the blood vessels
-the kidneys
Left side:
Hypothalamus detects hyperosmolarity and decrease in atrial receptor firing
This leads to the posterior pituitary gland to secrete ADH, or vasopressin, to bind to the V1 receptors
Causing blood vessels to constrict
Causing increased systemic vascular resistance
Ultimately increasing arterial pressure
Right side:
Angiotensin II and sympathetic stimulation sends message to hypothalamus for ADH to be released by posterior pituitary
ADH then will bind to V2 Receptors
Causing fluid reabsorption in the kidneys
Increasing blood volume and increasing arterial pressure

8. Osmotic Sensors & Baroreceptors
Work with ADH to maintain water metabolism
By sensors in the hypothalamus reacting to the ccn of particles in your blood
Na+, K+, Cl-, CO2, etc
Unbalanced /   sensors tell kidneys to store or release water to maintain a healthy range
Regulate body’s sense of thirst
When the particle ccn is unbalanced or when the BP is low, these osmotic sensors and baroreceptors tell the kidneys to store or release water to maintain a healthy balance

9. Aquaporins Specialized membrane channel proteins
Made up of single peptide chain consisting of about 270 aa
Facilitate water transport across cell membranes
At least 7 expressed in kidneys
AQP 1, 2, 3, 4, 6, 7, 11
Role in short- & long-term regulation of water balance and pathophysiology of water balance disorders

10. Aquaporin Distribution in the Kidneys
Aquaporin Group
Localization in Kidney
AQP 1
APM/BLM of proximal tubules and descending thin limbs
AQP 2
APM/VES of principal cells of collecting ducts
AQP 3
BLM of collecting ducts
AQP 4
BLM of medullary collecting ducts
AQP 6
Cortex, Medulla
AQP 11
Proximal tubule (Intracellular)
AQP: Aquaporin, APM: Apical membrane, BLM: Basolateral membrane, VES: Vesicles

11. AQP2 Cloned as an ADH-regulated water channel of CD
Basal state: AQP2 stored in intracellular vesicular compartment
With ADH stimulation, it moves quickly to apical membrane where it acts as water channel for the ccn of urine
ADH acts at V2 receptors in BLM of CD principal cells
Vasopressin acts at V2 receptors in basolateral membrane of the collecting ducts’ principal cells.  Next slide is the mechanism how it works

12. Aquaporin 2 (AQP2)
At the basolateral membrane, activation of adenyl cyclase with the help of the enzyme, adenylate cyclase,  production of cyclic Adenosine Monophosphate from ATP  cAMP then will bind to protein kinase A (PKA)  which activates the catalytic subunit of PKA  PKA phosphorylates transcription factors like cAMP responsive element-binding protein (CREB-P) and c-jun / c-fos for synthesis of AQP2 in the intracellular vesicle and possibly other membrane prots
 Binding of CREB-P and c-jun / c-fos proteins  increases gene transcription of AQP2  synthesis of AQP2 protein  which then enters the regulated trafficking sys
NOT SHOWN in diagram – there are microtubular motor prots and vesicle targeting receptors (VAMP-2, Syntaxin-4, and NSF) that possibly add specificity of AQP2 targeting apical membrane to increase water permeability

13. ADH works on medulla collecting ducts
-AQP3
-AQP4
 Rapid reabsorption of water

14. AVPR1A Receptor Protein-coding gene
Subfamily of G-protein coupled receptors
AVPR1B, V2R and OXT receptors
Mediates:
Vasoconstriction
Antidiuresis
ACTH release
Cell contraction and proliferation
Platelet aggregation
Release of coagulation factor
Glycogenolysis
By G proteins that stimulate a phosphatidylinositol-calcium second messenger system
OXT receptors => ADH works similar to oxytocin

15. Vasopressin V2 Receptor
AVPR2 gene provides for production of this protein
Located on Chromosome Xq28
ADH + V2 Receptor = trigger chemical reactions for body’s water balance control
Xq28 = located on long arm of X chrom, at position 28

16. When body’s fluid intake is low or when sweating, the body produces more ADH. As ADH reaches and binds to V2 receptor, it directs the kidneys to concentrate urine by reabsorbing some of the water back into the bloodstream via the AQP2 protein & lowering the serum sodium

17. Excess Production of ADH
SIADH
Symptoms:
Headache, Nausea, Vomiting
Associated with:
Leukemia, lymphoma, lung / pancreatic / bladder / brain cancers, systemic cancers that produce ADH, MS, Epilepsy, Acute intermittent porphyria, TB, dehydration, brain trauma, and surgery
Nephrogenic diabetes insipidus
 very dilute urine
Symptoms: excessive urination (polyuria), extreme thirst (polydipsia)
Syndrome of Inappropriate ADH
Porphyria – genetic disorder that affects heme production
Nephrogenic diabetes insipidus
-norm OR high ADH content in blood
-BUT kidney can’t respond to it  dilute urine
-UNLIKE diabetes mellitus – since that affects the level of insulin hormone in blood

18. Deficiency of ADH
May be due to compulsive water drinking or low blood serum osmolality
Central diabetes insipidus
 in production of ADH by hypothalamus or realease of ADH from pituitary gland
Symptoms: excessive urination (polyuria), extreme thirst (polydipsia), often tired since sleep interrupted by urination urges, clear, odorless and has low ccn of particles in urine
Lead to severe dehydration

19. Sources
“Antidiuretic Hormone (ADH) Test”
“Aquaporins: The renal channels”
“AVPR1A arginine vasopressin receptor 1A [Homo sapiens (human)]”
“AVPR1A Gene (Protein Coding)”
“AVPR2 Gene”
“Definition of Antidiuretic Hormone (ADH)”
Human Physiology, McGraw Hill
“Vasopressin”
“Vasopressin (Antidiuretic Hormone)”