Angiotensin II blockade with
saralasin in human
cirrhosis with
ascites is associated with a significant reduction in arterial pressure, indicating that endogenous
angiotensin II plays an important role in the maintenance of systemic hemodynamics in this condition. The aim of the current study was to investigate whether
vasopressin also contributes to the maintenance of arterial pressure in
cirrhosis with
ascites. The study was performed using three groups of cirrhotic rats with
ascites and three groups of control animals. The administration of
d(CH2)5Tyr(Me)AVP, a selective antagonist of the vascular effect of
vasopressin, to 10 cirrhotic rats induced a significant reduction in mean arterial pressure (from 94 +/- 4 to 85 +/- 4 mm Hg; P less than 0.001) and a significant increase in plasma
renin activity (from 24.3 +/- 4.9 to 34.3 +/- 5.9 ng/mL.h; P less than 0.02) and plasma
norepinephrine concentration (from 1474 +/- 133 to 2433 +/- 253 pg/mL; P less than 0.01). Similar results were observed following
saralasin administration in a second group of 5 cirrhotic rats [mean arterial pressure decreased from 97 +/- 4 to 85 +/- 5 mm Hg (P less than 0.0001); and plasma
renin activity and
norepinephrine concentration increased from 18.4 +/- 5.8 to 40.3 +/- 5.7 ng/mL.h (P less than 0.02) and from 1383 +/- 70 to 2312 +/- 334 pg/mL (P less than 0.05), respectively]. The simultaneous blockade of
angiotensin II and
vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure (from 97 +/- 6 to 74 +/- 6 mm Hg; P less than 0.05). No changes in arterial pressure were observed in the three groups of control rats. These findings indicate that endogenous
vasopressin is as important as
angiotensin II in the maintenance of arterial pressure in cirrhotic rats with
ascites and support the contention that arterial
hypotension is the initial event leading to the stimulation of the renin-angiotensin system and
vasopressin in this animal model of
cirrhosis.