Neurohormonal Activation especially AVP in Congestive Heart Failure

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

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

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

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

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

6. 1 2 But cardiac contractility↑ heart rate↑ cardiac output↑ systemic vasoconstriction↑ Tissue –perfusion pressure ↑ In long-term, progressing CHF, because NA in myocyte ↓↓ β-receptor desensitized Activation of Sympathetic Nervous System

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

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

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

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

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

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

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

14. the Vasopressin Receptor V1a vasoconstriction and myocardial hypertrophy Liver, vascular SM, platelets, adrenal cortex, kidney, brain V1b Corticotropin cells, anterior pituitary possibly kidney,adrenal medulla regulates the release of adrenocorticotropin hormone from the pituitary gland Renal collecting ducts V2 water and sodium regulation

15. V2 receptor in renal collecting duct AVP BV ventricular end-diastolic pressure ↑ EC Hyponatremia edema Collecting duct

16. V1a receptor in vascular SM preload ↑ afterload↑ AVP BV adverse hemodynamic changes

17. In addition vascular SM V1b V1a cardiac remodeling

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

19. 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

20. Thank You !