The Vicious Cycle of Chronic Congestive Heart Failure

Spironolactone

Overflow and Underfilling Hypotheses of Sodium and Water Retention in Cirrhosis

PERIPHERAL ARTERIAL VASODILATION

HYPOTHESIS

Peripheral Arterial

Vasodilation

Plasma Hormones

(AVP, Renin,

Aldosterone, NE)

Plasma Volume

COMPENSATED CIRRHOSIS(No Ascites)

DECOMPENSATED CIRRHOSIS

(Ascites)

Hepatorenal Syndrome

Normal

Hypothalamic AVP-mRNA of Control and Cirrhotic Rats

“I have ascites and have desire for water, Although I know this water will kill me.”

Rami(1226-1294 A.D.)

Effects of Non-Peptide AVP Antagonist in Liver Cirrhosis

Effect of V1-Vasopressin Antagonist on Arterial Blood

Pressure in Experimental Cirrhosis in Rats

ALDOSTERONE ANTAGONISM PROMOTES WEIGHT LOSS AND DISAPPEARANCE OF

ASCITES IN DECOMPENSATED CIRRHOSIS

PARAMETER

Death

Weight loss (lb)

Disappearanceof ascites

CONTROL(n-22)

7

6 + 2

4

SPIRONOLACTONE(n=21)

5

24 + 4

16

CIRRHOTIC PATIENTS

Gregory et al., 1977

Increased Distal Tubular Sodium Delivery with Mannitol

Resulted in a Marked Natriuresis During ANP Infusion

Urinary cGMP Increased Significantly During ANP and

ANP + Mannitol

Distal Sodium Delivery During Mannitol and ANP + Mannitol in

Cirrhotic Patients

Mean Arterial Pressure is Increased by Immersion Plus

Norepinephrine but not by Immersion Alone

Effect of Increased Arterial Circulatory Integrity to

Normalize Renal Water Excretion in Decompensated

Cirrhotic Patients

Correlation Between Increase in Systemic Vascular Resistance

and an Increase in Water Excretion in Cirrhotic Patients

Effects of Terlipressin and Albumin on Renal Function in

Hepatrorenal Syndrome

Cirrhosis – Arterial

Underfilling – Ascites

Effect of Chronic NOS Inhibition on Systemic Vascular

Resistance in Cirrhotic Rats with Ascites

Effect of NOS Inhibition for 7 Days on eNOS Protein Expression in Aortas and

Mesenteric Arteries in Cirrhotic Rats with Ascites

Effect of Chronic NO Synthesis Inhibition on Aortic cGMP in Cirrhotic Rats with Ascites

Effect of NOS Inhibition for 7 Days on Plasma Arginine

Vasopressin and Atrial Natriuretic Peptide in

Cirrhotic Rats with Ascites

Effect of NOS Inhibition for 7 Days on Water Excretion in Cirrhotic Rats with Ascites

Effect of NOS Inhibition for 7 Days on Plasma Renin Activity

and Aldosterone in Cirrhotic Rats with Ascites

Sodium Excretion is Increased by Chronic L-Name Treatment

in Cirrhotic Rats

Changes in Systemic

Hemodynamics and Plasma

Volume During

Pregnancy

Chronic L-NAME Treatment in Day 14 Pregnant Rats Returns

Cardiac Output and SVR to Nonpregnant Levels

Chronic L-NAME Treatment in Day 14 Pregnant Rats Returns GFR and RPF to Nonpregnant

Levels

Protein Expression of AQP 2 in Pregnancy

Effect of Vehicle and V2 Antagonist on Water Balance in

Pregnant Rats

PATHOPHYSIOLOGY OF WATER METABOLISMIN EDEMATOUS DISORDERS

NON-OSMOTIC VASOPRESSIN RELEASE

VASOPRESSIN V2 RECEPTOR

AQUAPORIN-2

INCREASED WATER PERMEABILITY OF COLLECTING DUCT

WATER RETENTION

CONGESTIVE CARDIAC FAILURE

CARDIAC OUTPUT

CIRRHOSIS

PERIPHERAL VASODILATION

PREGNANCY

V2 RECEPTOR

ANTAGONIST

Nitric Oxide