Neurohormonal Activation especially AVP in Congestive Heart Failure 陈宇寰 丁 宁 高 柳 郭华秋 韩国嵩 臧 鹏

Mechanisms of Heart Failure Heart failure Ventricle remodeling Neurohormonal activation Sustained etiological factors Or motivation

Neurohormonal Activation Neurohormonal Activation SNS RAAS Others AVP sympathetic nervous system renin-angiotensin-aldosterone system arginine vasopressin ET-1 TNF-αIL-6 adenosine

FIGURE 1 Neurohormonal activation in congestive heart failure. (Adapted from Braunwald Atlas of Heart Diseases Online. 4)

Neurohormonal Activation Neurohormonal Activation SNS RAAS Others AVP sympathetic nervous system renin-angiotensin-aldosterone system arginine vasopressin ET-1 TNF-αIL-6 adenosine

Activation of Sympathetic Nervous System 1 cardiac contractility↑ heart rate↑ cardiac output↑ 2 systemic vasoconstriction ↑ Tissue – perfusion pressure ↑ But In long-term, progressing CHF, because NA in myocyte ↓↓ β-receptor desensitized

Neurohormonal Activation Neurohormonal Activation SNS RAAS Others AVP sympathetic nervous system renin-angiotensin-aldosterone system arginine vasopressin ET-1 TNF-αIL-6 adenosine

Activation of Renin-Angiotensin System RAAS activation Renal vasoconstriction ADH release↑ Water-sodium retention RAAS activation Cadiac output vasoconstriction Preload and postload ↑

Neurohormonal Activation Neurohormonal Activation SNS RAAS Others AVP sympathetic nervous system renin-angiotensin-aldosterone system arginine vasopressin ET-1 TNF-αIL-6 adenosine

ARGININE VASOPRESSIN （ AVP ） circulating blood volume↓ baroreceptors osmolality of the extracellular fluid compartment changes osmoreceptors AVP release norepinephrine and angiotensin II.

ROLE OF AVP IN CIRCULATORY HOMEOSTASIS adrenocorticotropin secretion free-water absorption body osmolality↓, blood volume, blood pressure↑ a potent vasoconstrictor acts on the kidney to stimulate the conservation of water cell contraction and proliferation

FIGURE 3 Stimulation and production of arginine vasopressin. (Adapted from Braunwald Atlas of Heart Diseases Online 4 and J Am Coll Cardiol.15)

Role of AVP in CHF Overt CHF patients CHF but not overt healthy individuals AVP ?

the Vasopressin Receptor V1aV1a V 1b V2 V2 vasoconstriction and myocardial hypertrophy regulates the release of adrenocorticotropin hormone from the pituitary gland water and sodium regulation Liver, vascular SM, platelets, adrenal cortex, kidney, brain Corticotropin cells, anterior pituitary possibly kidney,adrenal medulla Renal collecting ducts

V 2 receptor in renal collecting duct Collecting duct EC AVP Hyponatremia edema ventricular end-diastolic pressure ↑ BV

V 1a receptor in vascular SM AVP adverse hemodynamic changes afterload↑ preload ↑ BV

In addition V1a V1b cardiac remodeling vascular SM

cardiac remodeling Long-term hemodynamic changes Heart failure cure V1a and V1a/V2 receptor antagonists

CONCLUSION low cardiac output and arterial pressure of CHF result in an abnormal and chronic activation of neurohormona l systems Activation of the SNS, RAAS, and AVP secretion results in vasoconstricti on, edema, and increased blood volume In the long term, can exacerbate LV dysfunction and accelerate progression of CHF Antagonism of AVP activity with V1a- selective and V1a/V2- selective receptor antagonists