Vasopressin Flashcards
Four different vasopressin receptors
V1R, V2R, V3R, the oxytocin receptor
How long does the synthesis, transport and storage of vasopressin take?
1-2 hours
Half-life of vasopressin
10-35 minutes
Three most potent stimuli for vasopressin (ADH) stimulation
Decreased ECV
Increased plasma osmolality
Decreased BP
Release of vasopressin inhibited by
Glucocorticoids
Low-dose opioids
Atrial natriuretic factor
GABA
Where in the brain are central osmoreceptors located?
Third ventricle
Where are peripheral osmoreceptors located?
Mesenteric and portal veins
T/F: Vasopressin receptors are G protein-coupled receptors
True
Hypovolemia and hypotension shift the osmolality-vasopressin response curve so that a ______ higher vasopressin level is required to maintain normal osmolality in hypotensive states
Higher
V1 receptors
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
T/F: Vasopressin also causes inactivation of the potassium ATP channels on vascular smooth muscle cells
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
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
Reduce blood flow
Increase GFR
V2 receptors
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
T/F: Most animals with hereditary NDI have mutations of the V2 receptor
True
How does V2 receptor activation alter coagulation
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
Effects of DDAVP admin
Vasodilation, release of vWF and factor VIII
V3 receptors
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
Oxytocin receptor
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
P2 receptors
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
How much AVP/vasopressin in storage in the pituitary can be readily released at once?
10-20%
After that, further release occurs at a much slower rate that results in a biphasic response to vasodilatory shock
Vasopressin- protein binding, volume of distribution, half life, clearance
NOT protein bound
Volume of distribution 140 mL/kg
Half life 24 minutes
Cleared by renal excretion (65%) and metabolism by tissue peptidases (35%)
Terlipressin half life
6 hours
Greater V1 receptor selectivity
Prolonged duration of action
Negative consequences of terlipressin administration
Peripheral cyanosis
Ischemia
Hypoxia
Serious or fatal respiratory failure
Selepressin
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.
Desmopressin acetate
Stimulates V2 receptors- antidiuretic and procoagulant effects
Dose dependent increase in fVIII and plasminogen factor
Comparison of epinephrine and vasopressin during CPR
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
Vasopressin may cause more vasoconstrictive effects in states of ____ and ____ compared to catecholamines
Acidosis
Hypoxia
Vasopressin secretion may be inhibited by
NO
High circulating levels of norepinephrine
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
True
Two types of vWD that DDAVP is not indicated for
Type IIB or platelet-type (pseudo) –> can lead to platelet aggregation and thrombocytopenia
Are repeated doses of DDAVP effective
No- tachyphylaxis develops
Onset of action for vWD is within 30 min, duration of action 2 hours
