Vasopressin – a.k.a. Anti-Diuretic Hormone (ADH) – allows kidney to secrete <1% as much fluid as is filtered

• Synthesis and Release – made by neuron cell bodies in the superoptic nucleus of the hypothalamus
• initially synthesized as a pre-prohomone (called propressophyisn) bound to a carrier peptide, neurophysin II
• cleaved into ADH (a 9 amino acid polypeptide ring) and neurophysin II in secretory granules
• secretory granules are transported along axon thru pituitary stalk, to nerve terminals in posterior pituitary
• released from pars nervosa and pituitary stalk – secretion from stalk occurs even if rest of pituitary is destroyed
• release of granules occurs via Ca⁺⁺ mediated exocytosis triggered by membrane depolarization (firing of the neuron)
• Neuroregulation of ADH Secretion – two mechanisms:
• (1) Osmoregulation – extremely sensitive mechanism – requires only 1% increase in osmolality to Ý ADH secretion
• Ý plasma osmolality causes osmoreceptors to shrink and fire action potentials, which leads to ADH release
• osmoreceptors may be the same neural cells which produce ADH, and may also trigger thirst
• (2) Hemodynamic Regulation – relatively insensitive – requires 10% volume reduction to Ý ADH secretion
• normal BV/BP inhibits ADH release through stimulation of stretch receptors in left atrium/pulmonary veins and baroreceptors in carotid sinus/aortic arch – signal carried by vagus nerve
• if blood volume/BP is decreased, the inhibitory signal disappears, and ADH secretion increases
• during severe volume reductions, this mechanism becomes very powerful and can override osmoregulation
• Hormonal Regulation of ADH Secretion – not as sensitive or as potent as neuroregulation
• cholinergic and b -adrenergic impulses stimulate ADH secretion; cortisol and thyroid hormone inhibit ADH secretion
• Target of ADH – 7-transmembrane receptors linked to Ga _s proteins Þ cAMP Þ PKA – several classes:
• V₁ receptors – on vascular endothelium; promote vasoconstriction and platelet aggregation in peripheral vasculature
• V₂ receptors – on nephron; cause transfer of aquaporin channels to luminal memb of collecting duct Þ H₂O reabs.
• V₃ receptors – on anterior pituitary; cause secretion of ACTH
• there are other receptors in the brain which currently have unknown function (possibly behavioral)
• Diseases Related to ADH:
• (1) Diabetes Insipidus – due to deficient ADH action Þ loss of free H₂O by the kidneys Þ constant thirst, water intake
• neurogenic diabetes insipidus – ß secretion due to brain pathology (tumor, etc.) – will respond to IV ADH
• treatment – intranasal long acting ADH (DDAPV)
• nephrogenic diabetes insipidus – ß response to ADH – will not respond to IV ADH
• familial – rare mutation in aquaporin channels
• other causes – hypokalemia/hypercalcemia, chronic renal failure, drugs (lithium, demeclocycline), enzyme deficiency, etc
• treatment – hydrochlorothiazide diuretic (to prevent hypernatremia)
• polydipsia/polyuria (esp. psychogenic) – looks like diabetes insipidus, but caused by excessive fluid intake
• involves low plasma osmolality – in true diabetes insipidus, plasma osmolality is high
• water deprivation test – when fluids are withheld, urine osmolality will change only in polydipsia/polyuria
• (2) SIADH (Syndrome of Inappropriate ADH secretion) – excessive ADH secretion leads to retention of free water
• Causes of SIADH:
• ectopic ADH secretion – usually tumors, especially oat cell carcinoma of the lung
• overstimulation of ADH secretion –frequently from pulmonary disorders (altered function of stretch receptors)
• other causes – drugs, stress, pain, psychosis (via adrenergic receptors), CNS disorders, etc
• retention of free H₂O makes SIADH #1 cause of hypo-osmolality and hyponatremia, the most common electrolyte imbalance in hospital patients; it is associated with a 60-fold increase in mortality
• edema is not typical because increased volume Þ ß aldosterone, Ý GFR, and Ý ANF Þ excretion of Na⁺ and H₂O
• symptoms – dependant on the absolute level and rate of fall of hypo-osmolality/hyponatremia
• weakness, confusion, muscle cramps, vomiting; may progress to coma and death; reflexes depressed
• diagnosis – six criteria:
• hypotonic extracellular fluid (hyponatremia)
• urine that is not maximally dilute
• high urine sodium
• patient is not dehydrated
• normal thyroid and adrenal function
• normal renal function
• treatment – if hyponatremia is acute, it is an emergency
• Na⁺ can be restored via hypertonic saline, but no more than 1 mM per hour (rapid Ý [Na⁺]Þ neuroligic problems)
• loop diuretic should be combined with normal saline to ensure neutral H₂O balance and positive Na⁺ balance
• chronic SIADH is usually treated with restriction of water intake; or ADH blocking drugs (demeclocycline)

• Synthesis, structure, release – identical to vasopressin except released from paraventricular nucleus and that oxytocin is bound to neurophysin I (pro-oxyphysin)
• Actions – urterine contractions in labor; smooth muscle contractions in lactation (oxytocin is non-essential in both)
• Stimulation – neural reflex arc in response to distension of genital tract, suckling; also through pain, anxiety, fear, etc.