The initiation phase of experimental acute renal failure: an evaluation of uranyl nitrate-induced acute renal failure in the rat.
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Biomedical subjects
Publications and source records attributed to W Flamenbaum.
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The effect of propranolol therapy on plasma renin activity and blood pressure control was evaluated in 35 uremic patients receiving intermittent center-based outpatient hemodialysis. Patients were determined to be either compliant or noncompliant with therapy based on the steady-state predialysis plasma propranolol concentration. Noncompliance occurred with remarkable frequency and was associated with persistent hyperreninemia and poorly controlled hypertension. Blood pressure control was significantly better in compliant patients, in whom plasma renin activity was generally, but not universally, suppressed. Propranolol can be effectively used in the management of hypertensive dialysis patients, but steady-state plasma propranolol levels should be measured to assess compliance in patients apparently refractory to treatment.
A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin II, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (Cin) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, Cin of one group being 18% of control, Cin of the other groups was less than 3% of control. The dose and binding capacity of the immune globulin used here were essentially the same as those reported in another study in which immunization was thought to be of prophylactic value in rats subjected to s.c. administered glycerol injections. Technologic differences unrelated to immunization are suggested to have caused the difference in results in the two studies, and it seems doubtful that circulating angiotensin plays a key role in the pathogenesis of myohemoglobinuric acute renal failure in the rat.
1. Sodium excretion, plasma renin acitivity (PRA), inulin clearance, total renal blood flow (RBF), renal cortical radiomicrosphere distribution and systemic administration of uranyl nitrate (19.9 mumol/kg body wt.; 10 mg/kg) in the dog. 2. During the 3 h of study after uranyl nitrate, urine flow remained stable or increased, sodium excretion increased approximately fivefold, renal vascular resistance increased threefold, and concordant decreases in RBF and inulin clearance to 40-50% of control values occured. At 3 h total cortical RBF decreased to 35% of control values and the ration of blood flow in outer to inner cortical zones also decreased, reflecting outer cortical ischaemia, PRA increased in the first hour after uranyl nitrate and slowly declined therafter, though not to control values. 3. Respiratory rate, heart rate, mean systemic blood pressure and cardiac output were unchanged after uranyl nitrate, demonstrating that the changes in renal vascular resistance occurred without a change in peripheral vascular resistance. 4. It is postulated that increased renin-angiotensin system activity mediates the change in renal haemodynamics and the consequent fall in glomerular filtration.
The effects of unilateral intrarenal arterial KCl infusion in dogs (12 mueq/kg per min) on bilateral renal function, renin secretory rates, and aldosterone excretion were studied. During KCl infusion, infused-side renal arterial plasma [K+] increased by 2.2 +/- 0.6 meq/liter. Systemic plasma [K+] simultaneously rose by 0.6 +/- 0.1 meq/liter. Plasma renin activity decreased 29 +/- 9%, and the decrease correlated with the increases in plasma [K+]. Renin secretory rate decreased bilaterally, the decrease being greater in each experiment on the infused side. Aldosterone excretion increased during KCl infusion by 72 +/- 17%, despite a decrease in plasma renin activity. With KCl infusion there was a bilateral increase in K+ excretion, and a positive correlation was observed between the net alterations in K+ and Na+ excretion. No significant alterations in systemic blood pressure, glomerular filtration rate, total renal blood flow, or intracortical renal blood flow distribution were observed. These studies suggest that K+ inhibits the release of renin by an intrarenal mechanism, which may be related to a K+-induced alteration in Na+ absorption.
In this study, rats recovering from glycerol-induced acute renal failure were found to be protected from mercury-induced nephropathy, and HgCl2 poisoning protected rats from developing myohemoglobinuric renal failure. In view of the widely disparate nature of the renal failure models used, refractoriness appears to relate to an altered sensitivity of the organism itself rather than reflecting resistance to a particular nephropathic challenge. Renal renin content of the rats at the time of rechallenge was normal or high, a finding which contrasts sharply with that of chronically saline-loaded animals which also are refractory to ARF but have a maximally suppressed renal renin content. Renal renin depletion is not essential to the prevention of acute renal failure in the rat.
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To evaluate the effect of Ca(++) on renin release, plasma renin activity (PRA) was measured after acute and chronic Ca(++) administration. 1% CaCl(2) was infused into one renal artery of 10 anesthetized dogs (0.3 mg/kg/min). The excreted fraction of filtered calcium (EF(ca++)) and EF(Na+) from the infused kidney were elevated (P < 0.04) during three successive 15-min infusion periods. Serum calcium concentration was significantly elevated (P < 0.001). Creatinine clearance, systemic arterial pressure, and renal blood flow did not change (P > 0.10). Compared to control (45 ng/ml/h+/-5.2 SE), renal venous PRA was suppressed (P < 0.0001) after infusion of Ca(++) for 15, 30, and 45 min (20 ng/ml/h+/-4.6, 16 ng/ml/h+/-4.0, and 13 ng/ml/h+/-2.7, respectively). 15 and 30-min after infusion, PRA did not differ from control (P > 0.20). Chronic Ca(++) loading was achieved in Sprague-Dawley rats by replacing drinking water with 1% CaCl(2) for 17 days. At sacrifice, serum Ca(++), Na(+), and K(+) of controls (n = 12) did not differ (P > 0.60) from Ca(++)-loaded rats (n = 12). Ca(++) excretion (467 mueq/24 h+/-51) was elevated (P < 0.001) compared to controls (85 mueq/24 h+/-12). PRA (8.6 ng/ml/h+/-1.4) and renal renin content of Ca(++)-loaded rats did not differ from controls (P > 0.80). However, after 8 days of sodium deprivation, both PRA and renal renin content of calcium-loaded animals were significantly lower than the respective values in pair-fed controls (P < 0.005). During the period of sodium deprivation, calcium-drinking animals were in greater negative sodium balance than controls (P < 0.005). The data are consistent with the hypothesis that acute and chronic calcium administration inhibit renin secretion.
The intrarenal gradient of renin activity was determined in rats by using superficial (S) and deep (D) cortical juxtaglomerular apparatuses (JGA's), identified and microdissected after silicone-rubber compound injection. Angiotensin generated from single JGA's using partially purified sheep renin substrate was quantified by rat bioassay. When, in rats on a normal NaCl diet, silicone-rubber was injected into a carotid artery, alone or with abdominal aorta catheterization, S:D renin activity ratios were 1.18+/-0.08 (SEM) and 1.21+/-0.12, respectively. The S:D renin activity ratios obtained when silicone-rubber was injected into the abdominal aorta (2.52+/-0.09) or a chronic carotid artery catheter (3.44+/-0.40) were significantly higher (P < 0.001). The lower S:D renin activity ratios after carotid artery manipulation were due to significantly higher D-JGA renin activities. This increased D-JGA renin activity and the lack of a renin gradient appear to be related to acute carotid artery manipulation. Alterations in JGA renin activity were examined relative to NaCl intake. 2 wk after high-NaCl diet the absolute net renin activity decreased (P < 0.001) more in S (5.84+/-0.11 ng AI.JGA(-1).h(-1)) than D (1.73+/-0.06 ng AI.JGA(-1).h(-1)) JGA's, and the intrarenal renin gradient was lost (S:D-JGA renin activity, 1.00+/-0.07), as compared to the regular NaCl diet. 2 wk of a low-NaCl diet resulted in a greater (P < 0.01) increase in S (14.28+/-1.47 ng AI.JGA(-1).h(-1)) than D (9.62+/-1.19 ng AI.JGA(-1).h(-1)) JGA renin activity and a renin gradient (S:D-JGA renin activity) of 1.75+/-0.12. These results demonstrate that NaCl intake clearly influences total JGA renin content and may also affect the relative intrarenal distribution of renin activity.
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