saralasin and Kidney-Failure--Chronic

Topics: Adult; Angiotensin II; Animals; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Propranolol; Rats; Renin; Saralasin

Topics: Aldosterone; Arginine Vasopressin; Blood Pressure; Cardiac Output; Heart Rate; Hemodynamics; Humans; Hypertension, Malignant; Kidney Failure, Chronic; Norepinephrine; Phentolamine; Renin; Saralasin; Stroke Volume; Vascular Resistance

Topics: Adult; Angiotensin II; Blood Pressure; Blood Volume; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Infusions, Parenteral; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Renal Dialysis; Renin; Saralasin

Topics: Adolescent; Adult; Aldosterone; Angiotensin II; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Renin; Saralasin

The "effective" contribution of angiotensin II in blood pressure regulation was investigated in 6 patients on maintenance hemodialysis who were hypertensive at the time of the study (MAP 133 +/- 5 mmHg). Saralasin, a specific angiotensin II inhibitor, was infused at 0.5 and 2.5 microgram/kg/mn three hours before andone hour after hemodialysis. Before hemodialysis, a mean arterial pressure decrease of 13.2 to 19 p. 100 was obtained in 5 patients, arterial pressure being normalized in three of them. After hemodialysis, saralasin induced a normalization of arterial pressure in these 5 subjects. One patient, who was resistant to the saralasin infusion before and after the hemodialysis procedure, can be considered as purely volume-dependent. The renin-angiotensin system is probably one of the primary determinant of dialysis-resistant hypertension. However, a negative response to saralasin should encourage to control hypertension by more vigorous ultrafiltration during dialysis.

Topics: Adult; Angiotensin II; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Saralasin

Topics: Antihypertensive Agents; Body Water; Clonidine; Diazoxide; Ethacrynic Acid; Furosemide; Guanethidine; Humans; Hypertension, Renal; Kidney Failure, Chronic; Methyldopa; Renal Dialysis; Renin; Reserpine; Saralasin; Teprotide; Vasodilator Agents

The angiotensin antagonist saralasin was infused both before and 10 hrs after dialysis in 10 hypertensive and 4 normotensive patients hemodialyzed for terminal renal failure. A significant increase in mean arterial pressure (MAP) and total peripheral resistance (TPR) without change in cardiac output measured by impedance cardiography were observed during the first few minutes of saralasin infusion. MAP and TPR decreased during the second half of the infusion in 4 hypertensive patients and remained at the preinfusion levels in 6 hypertensive and 4 normotensive patients. Plasma renin activity (PRA) was significantly higher in patients in whom MAP fell both before and after hemodialysis. There was a significant correlation between PRA before saralasin and the fall in MAP and TPR. The fall in MAP in 4 of 10 hypertensive patients demonstrates that inappropriately high renin and angiotensin levels are involved in the pathogenesis of hypertension in some patients with terminal renal failure. Volume factors are probably of primary importance in the other patients.

Topics: Adult; Aged; Angiotensin II; Blood Pressure; Cardiac Output; Female; Hemodynamics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pulse; Renal Dialysis; Saralasin

This report describes macromolecules that bind (des-aspartic acid1)-angiotensin II, the des aspartic acid1 derivative of angiotensin I, and several biologically active and inactive analogues of these polypeptides. The macromolecules were found in the plasma of approximately 2 per cent of ambulatory adults and hospitalized children and 32 per cent of the patients at two institutions for the mentally retarded. The binding properties of these macromolecules were studied by incubating with peptides labeled with 125iodine, and separating bound from free labeled peptide using small gel filtration columns. The peptide-binding macromolecules from several patients were compared. They showed very similar specificity for a group of arginyl peptides of the des-aspartyl1-angiotensin sequence. The plasma binders differed from one another in their optimum pH and their mobility in electrophoretic fields. Those with more acid pH optima displayed more rapid electrophoretic mobility. The binders fell into two classes based on apparent molecular weight, approximately 140,000 and 250,000. Those with the higher apparent molecular weight contained a large proportion of binder that could be precipitated with antiserum to human IgA. Kinetic measurements showed that the plasma binders were somewhat heterogeneous with respect to affinity for (des-asp1)-angiotensin, with apparent association constants ranging from 10(7) to 10(8) M-1. Binding activity was labile to heat, and to treatment with pepsin or trypsin. It was inhibited by calcium, protamine, streptomycin, and some other cationic compounds. The plasma peptide binder differed in specificity and molecular weight from soluble angiotensin-binding molecules extracted from tissues, and from properties expected of a receptor for angiotensin. These macromolecules may be useful reagents for measuring (des-asp1)-angiotensins. Their presence in plasma samples may interfere with angiotensin assays in some circumstances.

Topics: Angiotensin II; Chromatography, Gel; Electrophoresis, Starch Gel; Humans; Hydrogen-Ion Concentration; Intellectual Disability; Kidney Failure, Chronic; Kinetics; Macromolecular Substances; Neoplasms; Osmolar Concentration; Peptides; Protein Binding; Saralasin

1. A P113 Saralasin infusion test was performed in 10 patients on long-term regular hemodialysis. Six patients were considered to have hypertension resistant to dialysis treatment and 4 had their arterial pressure controlled by dialysis. 2. Five out of 6 resistant and 3 out of 4 responsive patients had a positive response to Saralasin associated with a normalization of diastolic arterial pressure. 3. The value of the Saralasin infusion test to pre-select the patients for bilateral nephrectomy is discussed and it is felt that a negative test may be of more value in encouraging more aggressive ultrafiltration in hypertension apparently resistant to dialysis therapy.

Topics: Adult; Angiotensin II; Female; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Renal Dialysis; Renin; Saralasin

The angiotensin antagonist saralasin (1-sar-8-ala-angiotensin II) was given to 27 patients with different forms of secondary hypertension. The blood pressure fell in 6 of 7 patients with renal artery stenosis and in 4 of 10 patients with terminal renal failure on regular hemodialysis. No change or a rise in blood pressure was observed in 3 patients with Cushing's syndrome, 4 patients with primary aldosteronism, 3 patients with hypertension and a unilateral small kidney of other than renovascular origin, and 6 patients with terminal renal failure. It can be concluded from the results that angiotensin II is involved in the pathogenesis of renovascular hypertension and in some cases of hypertension accompanying chronic renal failure.

Topics: Angiotensin II; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension, Renal; Kidney Failure, Chronic; Renal Artery Obstruction; Saralasin

The effect of saralasin in lowering blood pressure and plasma aldosterone concentration in normal subjects, both sodium-replete and sodium-deplete, and in patients with various forms of hypertension, is closely related to the basal plasma angiotensin II concentration. These findings confirm and extend earlier studies of angiotensin II/arterial pressure and angiotensin II/aldosterone dose-response curves. They also emphasize the importance of the renin-angiotensin system in the control of aldosterone in sodium depletion and in renal hypertension.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Diet; Humans; Hyperaldosteronism; Hypertension; Kidney Failure, Chronic; Male; Renal Artery Obstruction; Renin; Saralasin; Sodium; Time Factors