What is vasopressin?

What is Vasopressin

Vasopressin is a potent nonapeptide vasopressor hormone released by the posterior pituitary gland in response to hypotension and hypernatremia, used clinically to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. 1, 2

Chemical Structure and Formulation

• Vasopressin is a polypeptide hormone with the chemical name Cyclo (1-6) L-Cysteinyl-L-Tyrosyl-L-Phenylalanyl-L-Glutaminyl-L-Asparaginyl-L-Cysteinyl-L-Prolyl-L-Arginyl-L-Glycinamide 2
• Molecular formula: C46H65N15O12S2 with a molecular weight of 1084.24 Daltons 2
• Available as a sterile, clear solution at 20 units/mL for intravenous administration after dilution 2
• One mg is equivalent to 530 units 2

Physiologic Role and Regulation

• Vasopressin is synthesized in the hypothalamus and released from the posterior pituitary in response to increased plasma osmolality, decreased arterial pressure, and reductions in cardiac volume 3
• Essential for cardiovascular homeostasis, acting on the kidney to regulate water resorption, on the vasculature to regulate smooth muscle tone, and as a central neurotransmitter modulating brainstem autonomic function 4
• Actively involved in blood pressure regulation to the same degree as catecholamines and the renin-angiotensin-aldosterone system, especially in stressful situations 5

Receptor Mechanisms

Vasopressin stimulates a family of receptors with distinct functions 1:

• V1a receptors: Mediate vasoconstriction through vascular smooth muscle contraction; this is catecholamine-independent, explaining why vasopressin complements norepinephrine in septic shock 1, 3
• V1b receptors: Responsible for ACTH release and modulation of mood and behavior 1, 6
• V2 receptors: Produce anti-diuretic effects through water reabsorption in the kidney 1, 6
• Oxytocin receptors: Cause vasodilation 1

Cellular Signaling Pathways

• V1 receptors are linked to two intracellular messengers: 1,2 diacylglycerol and 1,4,5 inositol triphosphate, which stimulate protein kinase C and calcium-calmodulin kinase in the presence of calcium 5
• V2-renal receptors stimulate cyclic AMP production, activating protein kinase A, which alters the actin network and causes water molecule reabsorption 5

Paradoxical Effects

• Vasopressin paradoxically induces synthesis of nitric oxide (NO) 1
• NO may limit vasopressin's vasoconstriction while preserving renal perfusion 1
• However, NO may also contribute to vasopressin/NO-induced cardiac depression 1

Clinical Use in Shock States

Rationale for Use in Septic Shock

• Vasopressin deficiency occurs in early septic shock due to depletion of vasopressin stores and inadequate synthesis and release from the hypothalamic-pituitary axis 1
• A relative deficiency of vasopressin has been found in prolonged vasodilatory shock, and exogenous vasopressin has marked vasopressor effects even at doses that would not affect blood pressure in healthy individuals 4
• Vasopressin's action is independent of catecholamine receptor stimulation, so its efficacy is not affected by alpha-adrenergic receptor down-regulation often seen in septic shock 1

Dosing and Effects

• Low-dose vasopressin infusion of 0.01–0.04 units/min increases blood pressure and decreases norepinephrine requirements 1
• Vasopressin increases MAP, SVR, and urine output in patients with vasodilatory septic shock and hyporesponsiveness to catecholamines 1
• Vasopressin may have a greater impact on glomerular filtration pressure through a preferential effect on efferent arteriole, explaining greater urine output and creatinine clearance at the same blood pressure compared to norepinephrine 1

Important Clinical Caveats

• Vasopressin is not currently recommended for treatment of cardiogenic shock; it should not be used without ScvO2/CO monitoring 1
• The Vasopressin and Septic Shock Trial showed no difference in 28-day mortality between low-dose vasopressin and norepinephrine 1
• Vasopressin deficiency and its anti-diuretic effects only become apparent later, during septic shock recovery, with about 60% of patients having inadequate vasopressin responses to an osmotic challenge 5 days post recovery 1
• At low doses, vasopressin has modest effects on splanchnic circulation, but at high doses it markedly impairs it 1

Additional Hemostatic Effects

• Vasopressin modifies human hemostasis via platelet aggregation, stimulation of the three fractions of factor VIII, factor XII, and fibrinopeptide A 5
• These properties have been used to treat hemostasis abnormalities seen in Von Willebrand's disease and hemophilia 5

Potential Adverse Effects

• In pathological conditions such as stroke, traumatic brain injury, subarachnoid hemorrhage, and liver disease, vasopressin can exacerbate brain edema 6
• Oversecretion of vasopressin unleashes deleterious pathways leading to hyponatremia and brain edema 6
• Conflicting reports regarding its use as a primary agent in post-cardiac surgery vasoplegic syndrome include dysrhythmia and myocardial infarction 1