Vasopressin

Question 1

Four different vasopressin receptors

Answer 1

V1R, V2R, V3R, the oxytocin receptor

Question 2

How long does the synthesis, transport and storage of vasopressin take?

Answer 2

1-2 hours

Question 3

Half-life of vasopressin

Answer 3

10-35 minutes

Question 4

Three most potent stimuli for vasopressin (ADH) stimulation

Answer 4

Decreased ECV
Increased plasma osmolality
Decreased BP

Question 5

Release of vasopressin inhibited by

Answer 5

Glucocorticoids
Low-dose opioids
Atrial natriuretic factor
GABA

Question 6

Where in the brain are central osmoreceptors located?

Answer 6

Third ventricle

Question 7

Where are peripheral osmoreceptors located?

Answer 7

Mesenteric and portal veins

Question 8

T/F: Vasopressin receptors are G protein-coupled receptors

Answer 8

True

Question 9

Hypovolemia and hypotension shift the osmolality-vasopressin response curve so that a ______ higher vasopressin level is required to maintain normal osmolality in hypotensive states

Answer 9

Higher

Question 10

V1 receptors

Answer 10

Found on vascular smooth muscle
Cause vasoconstriction in most vascular beds
Mediated by Gq protein coupled activation of the phospholipase C and phosphoinositide pathways

Increased levels of inositol phosphate and diacylglycerol activate voltage gated calcium channels –> increased intracellular calcium and subsequent vasoconstriction

Question 11

T/F: Vasopressin also causes inactivation of the potassium ATP channels on vascular smooth muscle cells

Answer 11

True-
Opening of these channels (as occurs during acidosis or hypoxia) allows an efflux of potassium from the endothelial cells, subsequent hyperpolarization, and prevention of calcium entry into the cells. SO by inactivating them, depolarization occurs, opening the calcium channels and causing vasoconstriction

Question 12

V1 receptors in the kidney lead to ___ blood flow to the inner renal medulla and selectively cause vasoconstriction of the efferent arterioles leading to ____ in GFR

Answer 12

Reduce blood flow

Increase GFR

Question 13

V2 receptors

Answer 13

Found on the basolateral membrane in the distal tubule and in the principal cells of the cortical and medullary collecting duct

Coupling with Gs signaling pathway increases intracellular cyclic adenosine monophosphate (cAMP) which triggers fusion of the aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principle cells, to increase water reabsorption

Question 14

T/F: Most animals with hereditary NDI have mutations of the V2 receptor

Answer 14

True

Question 15

How does V2 receptor activation alter coagulation

Answer 15

Stimulates release of PLT from bone marrow
Enhances release of vWF and fVIII from endothelial cells
Causes mild increase in activity of factor VIII-related antigen and ristocetin cofactor

Question 16

Effects of DDAVP admin

Answer 16

Vasodilation, release of vWF and factor VIII

Question 17

V3 receptors

Answer 17

Located in the anterior pituitary - activate Gq protein to release intracellular calcium after activation of phospholipase C and the phosphoinositol cascade

Stimulates the release of ACTH

These receptors are responsible for ADH’s actions in the neuro system- neurotransmitter of modulator of memory, blood pressure, body temperature, sleep cycles, and release of pituitary hormones

Question 18

Oxytocin receptor

Answer 18

Nonselective vasopressin receptor with equal affinity for both vasopressin and oxytocin

Smooth muscle contraction of myometrium and mammary myoepithelial cells

ADH also acts on oxytocin receptors in the umbilical vein, aorta, pulmonary after where it causes a NO mediated vasodilation
Stimulation of cardiac oxytocin receptors results in release of ANP

Question 19

P2 receptors

Answer 19

Also stimulated by vasopressin/ADH

Purinoreceptors (ATP receptors) - activation leads to vasodilation mediated by nitric oxide and prostacyclin

P2 receptors are also positive inotropic agents without direct effects on HR

Question 20

How much AVP/vasopressin in storage in the pituitary can be readily released at once?

Answer 20

10-20%

After that, further release occurs at a much slower rate that results in a biphasic response to vasodilatory shock

Question 21

Vasopressin- protein binding, volume of distribution, half life, clearance

Answer 21

NOT protein bound
Volume of distribution 140 mL/kg
Half life 24 minutes
Cleared by renal excretion (65%) and metabolism by tissue peptidases (35%)

Question 22

Terlipressin half life

Answer 22

6 hours
Greater V1 receptor selectivity
Prolonged duration of action

Question 23

Negative consequences of terlipressin administration

Answer 23

Peripheral cyanosis
Ischemia
Hypoxia
Serious or fatal respiratory failure

Question 24

Selepressin

Answer 24

Effective vasopressor substitute for norepinephrine by maintenance of MAP, reduction of vascular leak and edema formation, and shortening the duration of shock. No improvement in outcomes however compared to norepinephrine in humans.

Question 25

Desmopressin acetate

Answer 25

Stimulates V2 receptors- antidiuretic and procoagulant effects

Dose dependent increase in fVIII and plasminogen factor

Question 26

Comparison of epinephrine and vasopressin during CPR

Answer 26

No benefit of vasopressin with or without epinephrine when compared with epinephrine alone

No survival benefit to use of vasopressin vs. low dose epinephrine

** dose used was often lower than the recommended dose of 0.8 U/kg

Question 27

Vasopressin may cause more vasoconstrictive effects in states of ____ and ____ compared to catecholamines

Answer 27

Acidosis
Hypoxia

Question 28

Vasopressin secretion may be inhibited by

Answer 28

NO
High circulating levels of norepinephrine

Question 29

T/F: Vasopressin therapy may reduce the rate of progression of AKI to renal failure and decrease the requirements for renal replacement therapy in critically ill human patients

Answer 29

True

Question 30

Two types of vWD that DDAVP is not indicated for

Answer 30

Type IIB or platelet-type (pseudo) –> can lead to platelet aggregation and thrombocytopenia

Question 31

Are repeated doses of DDAVP effective

Answer 31

No- tachyphylaxis develops
Onset of action for vWD is within 30 min, duration of action 2 hours