saralasin and Kidney-Diseases

Cyclosporine-induced nephrotoxicity (CIN) was studied in rats treated for 7 days with cyclosporine (10 mg x kg-1 x day-1 im) or vehicle (CON). CIN rats displayed characteristic reductions in glomerular filtration (GFR) and renal blood blood flow (RBF), and electron microscopy showed injury to proximal cells. Metabolic studies (7 day) showed significantly lower renal sodium excretion in conscious CIN rats compared with CON. In anesthetized rats at similar blood pressures, nephron GFR (SNGFR) was lower in CIN than CON, but fractional Na reabsorption was similar. In CIN, SNGFR, measured proximally to block flow to the sensing site of tubuloglomerular feedback (TGF) at the macula densa, was not significantly different than distal SNGFR. The rate of distal fluid delivery was significantly lower in CIN than in CON. Inhibition of the renin-angiotensin system (RAS) with captopril (CAP, 10 mg/kg iv), or saralasin (SAR, 0.3 mg x kg-1 x h-1 iv) caused marked arterial hypotension in CIN and a fall in renal vascular resistance (RVR). With arterial pressure controlled, CAP or SAR increased GFR and RBF, and reduced RVR in CIN, but did not reverse the renal deficits compared with similarly treated CON. RBF autoregulation in CIN was impaired between 90 and 140 mmHg but was partially restored by CAP. We conclude that both the filtered load and excretion rate of sodium in CIN are significantly reduced compared with controls, that SNGFR in CIN is not depressed by TGF in response to elevated distal fluid delivery, and that the RAS is not a primarily mediator of the renal vasoconstriction in CIN.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Cyclosporins; Glomerular Filtration Rate; Hemodynamics; Homeostasis; Kidney; Kidney Diseases; Kidney Tubules; Male; Rats; Regional Blood Flow; Renin; Saralasin; Sodium; Time Factors

The effect of an intravenous infusion of saralasin in a rising dosage on blood pressure, central haemodynamics, forearm blood flow and venous distensibility was tested in 11 subjects with chronic non-uraemic renal disease. Only 1 subject had an elevated resting plasma renin activity, and in him saralasin produced a drop in systolic and diastolic blood pressures due to a decrease of the total peripheral vascular resistance whereas the plasma renin activity markedly rose. Among the remaining 10 subjects, whose plasma renin activity was within the normotensive range, blood pressure rose transiently in 3, with the lowest dose of aralasin, due to an increase in the total peripheral vascular resistance. Both these parameters returned to the control level when continuing the infusion and increasing its dosage. Excluding this initial period from the analysis, no relevant change, even with a more than tenfold increase in the saralasin dosage and a duration of the infusion of 1 h, was found in the following: blood pressure, cardiac and stroke index, heart rate, total peripheral vascular resistance, central and peripheral venous pressures, forearm blood flow and vascular resistance, forearm blood volume and venous distensibility. The haemodynamic response to the Valsalva manoeuvre remained unaffected by saralasin. It is concluded that angiotensin plays an active role in changing the haemodynamics and in elevating the blood pressure in subjects with chronic non-uraemic renal disease only in those cases where plasma renin activity is raised.

Topics: Adult; Angiotensin II; Blood Pressure; Chronic Disease; Female; Forearm; Heart Rate; Humans; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Regional Blood Flow; Renin; Saralasin; Vascular Resistance

Ten patients with hepatorenal syndrome were evaluated before and after creation of a side-to-side portacaval shunt or insertion of a peritoneovenous shunt, procedures which produced an increase in plasma volume and cardiac output. In the seven patients who survived surgery, renal function improved significantly, plasma renin activity fell from high to normal levels, and low levels of plasma renin substrate increased. Prior to surgery, blockade of angiotension II by saralasin produced hypotension and an increase in plasma renin activity, whereas after surgery, saralasin had no effect on blood pressure or renin. Our findings suggest that decreased "effective" plasma volume may be important in the stimulation of renin release and possibly in the pathophysiology of renal failure in the hepatorenal syndrome.

Topics: Angiotensinogen; Blood Pressure; Creatinine; Female; Hemodynamics; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Plasma Volume; Portacaval Shunt, Surgical; Renin; Saralasin

Topics: Glomerular Filtration Rate; Glomerulonephritis; Hemodynamics; Humans; Hypertension, Renovascular; Kidney Diseases; Lupus Erythematosus, Systemic; Methods; Nephritis; Saralasin

Topics: Angiotensin II; Blood Pressure; Humans; Hyperplasia; Hypertension, Renal; Kidney; Kidney Diseases; Regional Blood Flow; Renal Artery Obstruction; Renal Veins; Renin; Saralasin

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.

Topics: Adolescent; Adult; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Female; Humans; Hypertension; Hypertension, Renal; Kidney Diseases; Male; Middle Aged; Oligopeptides; Renin; Saralasin; Sodium; Teprotide