saralasin and Liver-Cirrhosis

We have studied the effect of angiotensin-II blockade with saralasin on the cardiovascular and hepatic hemodynamics and on the renin-angiotensin-aldosterone system in fourteen patients with cirrhosis and ascites. Control measurements showed that most of the patients had a low mean arterial pressure, high plasma volume, normal or high cardiac index, low peripheral resistance and high plasma renin activity and aldosterone concentration. The wedged hepatic venous pressure was increased in each patient and the estimated hepatic blood flow was normal in most of them. Overall, saralasin induced a significant reduction of the mean arterial pressure, cardiac index and peripheral resistance. The decrease of the peripheral resistance was greater than that of the cardiac index. Six of the patients developed a marked reduction of the mean arterial pressure with low doses of saralasin (1--2.5 microgram/kg/min), and they had significantly higher plasma renin activity and lower mean arterial pressure than the remaining eight patients who showed a slight or no hypotensive response in spite of infusing saralasin up to a dose of 10 micrograms/kg/min. Overall, the decrease of the mean arterial pressure correlated directly with the baseline values of plasma renin activity. Angiotensin-II blockade induced a significant reduction of the wedged hepatic venous pressure. The hepatic blood flow did not show any significant change. The decrease of the wedged hepatic venous pressure was directly related to the reduction of the mean arterial pressure and also to the control plasma renin activity. Our study indicates that in most patients with cirrhosis, ascites and high plasma renin activity, arterial pressure is maintained by the effect of endogenous angiotensin II on the peripheral vasculature, and we suggest that a pre-existing arterial hypotension secondary to an arteriolar vasodilatation is the cause of renin release in these patients. Our results also show that angiotensin-II blockade is accompanied by a reduction of the post-sinusoidal hepatic vascular resistance.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Cardiac Output; Hemodynamics; Humans; Liver Circulation; Liver Cirrhosis; Renin; Renin-Angiotensin System; Saralasin; Vascular Resistance

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Bartter Syndrome; Child; Diet, Sodium-Restricted; Female; Furosemide; Humans; Hydrocortisone; Hypertension; Liver Cirrhosis; Male; Middle Aged; Renin; Saralasin

In an attempt to evaluate the role of renin-angiotensin system in the contols of blood pressure and aldosterone secretion in the patients with cirrhosis and asictes, 7 patients were infused of an antagonist of angiotensin II, Sar-1 Ile-8 angiotensin II, intravenously to inhibit the action of renin-angiotensin system and to observe changes in arterial pressure and plasma aldosterone. In 1 patient with recent onset of severe ascites and high plasma renin activity, blood pressure and plasma aldosterone decreased during the infusion. In contrast, mild rise in blood pressure and various changes in plasma aldosterone were observed in the other 6 patients with normal plasma renin activity. These results suggest variable angiotensin dependency in the controls of blood pressure and plasma aldosterone in the patients with cirrhosis and ascites according to the stage of the disease, the states of sodium and water balance and/or palasma renin activity.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Ascites; Blood Pressure; Depression, Chemical; Female; Humans; Infusions, Parenteral; Liver Cirrhosis; Male; Middle Aged; Renin; Saralasin

1-Sar-8-ala angiotensin II (saralasin) was infused intravenously in graded doses of from 0.1 to 10 mug/kg/min to five patients with cirrhosis and ascites after three days of restricted sodium intake. In each patient blockade of AII by saralasin produced a marked fall in blood pressure, a rise in plasma renin activity (PRA) and plasma renin concentration (PRC) and, in four of the five, a fall in plasma aldosterone (PA). The rise in PRA and PRC correlated poorly with changes in blood pressure. The effects of saralasin rapidly reversed after cessation of the infusion. Plasma volume was normal or high in each case. Three patients were mildly hypotensive in the control state, and all five were resistant to the pressor effect of infused AII. After three days of salt loading, the above effects of saralasin were diminished but not abolished. In four normal subjects, after salt depletion, saralasin infusion induced qualitatively similar but much smaller changes in blood pressure, PRA and PRC. In two cirrhotic patients without ascites, after salt depletion, saralasin infusion caused a rise in blood pressure with no significant changes in PRA, PRC or PA. These results provide evidence that in patients with cirrhosis and ascites circulating AII is active in support of blood pressure, in direct suppression of renal renin release, and in stimulation of aldosterone release.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Chronic Disease; Humans; Liver Cirrhosis; Renin; Saralasin

Infusion of the angiotensin-II-antagonist saralasine led in one patient with Bartter's syndrome and one patient with decompensated hepatic cirrhosis, both of whom had a markedly raised plasma renin activity, to a fall in systolic and diastolic blood pressure. The results indicate that in normotensive patients a raised angiotensin II concentration in blood is haemodynamically important for the level of blood pressure if plasma renin activity is raised. In normotensives with normal plasma renin activity saralasine in the usual dosage (4.2 mug/kg-min) does not influence the blood pressure.

Topics: Adult; Aldosterone; Angiotensin II; Bartter Syndrome; Blood Pressure; Diuresis; Female; Heart Rate; Humans; Hyperaldosteronism; Kidney; Liver Cirrhosis; Male; Middle Aged; Renin; Saralasin

In order to study the role of renin in regulating blood pressure in normotensive states, saralasin (P113) was infused into normal subjects and patients with cirrhosis of the liver and ascites. In normal subjects on a normal sodium intake, P113 infusion had no effect on blood pressure. Only after the combined stress of a low sodium diet and the upright position did P113 lower the blood pressure. In two of the six cirrhotic patients, P113 caused a significant decrease in BP in the supine position. There was no consistent effect of the P113 infusion on plasma aldosterone or plasma renin activity in the normal or cirrhotic subjects.

Topics: Aldosterone; Blood Pressure; Diet; Humans; Liver Cirrhosis; Posture; Pulse; Renin; Saralasin; Sodium; Time Factors