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 factorsOr 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 Water-sodium retentionretention

RAAS activationCadiac 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

V1a

V1b

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

V2 receptor in renal collecting duct

Collecting

duct

EC

AVP

Hyponatremiaedema

ventricular end-diastolic pressure ↑

BV

V1a 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 failureHeart 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 neurohormonal systems

Activation of the SNS, RAAS, and AVP secretion results in vasoconstriction, 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