-Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II. inflammation; angiotensin receptor; autoimmune INFLAMMATION AND IMMUNE SYSTEM dysregulation are recognized as prominent contributors to the development and progression of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder associated with a high risk for the development of renal and cardiovascular disease, which are major causes of mortality in these patients (43). Almost all patients with SLE have at least some evidence of renal damage on biopsy (4, 11), and measures of declining renal function, including elevated serum creatinine and blood urea nitrogen or reduced filtration fraction, are commonly reported (11,20,28).The renin-angiotensin system (RAS) is well known for its critical role in renal hemodynamic control and blood pressure regulation and is a common therapeutic target in patients with SLE. Although renal dysfunction and blockade of the RAS system are common to patients with SLE, renal hemodynamic responses to ANG II have not been previously investigated. In the present study, we tested the hypothesis that during SLE, there is an enhanced renal hemodynamic response to acute infusion of ANG II. This hypothesis was tested using an experimental mouse model of SLE.The New Zealand Black/White F1 hybrid (NZBWF1) is an established and widely used model of lupus nephritis (8). Like humans with SLE, female NZBWF1 mice exhibit declining renal function with age (5, 23, 29, 42), and we previously reporte...

Single doses of decoquinate-3-14C were administered orally to colostomized chickens. Minor amounts (0.6 and 1.1 %) of radioactivity were excreted in the urine, but most of the radioactivity appeared in the feces or remained in the intestinal tract at 24 hr. Decoquinate-J-14C was orally administered to intact chickens for 3 successive days. The radioactivity was readily eliminated through the feces with no apparent retention of the compound. The radioactive components of the excreta were solubilized by successive extractions with ethanol and formic acid and were analyzed by thin-layer chromatography. Only 2.6% of the radioactive dose was metabolized to nondecoquinate components. The concentration of radioactivity in the bile was at least 30 times that in urine and blood. Thus, the bile appears to be implicated in the elimination of the absorbed compound. Decoquinate-14C given to chickens orally induced tissue residues throughout the bird body. When birds were medicated on successive days with decoquinate, a plateau of tissue residues occurred within 3 days. There was no accumulation of residue in any tissues examined.

Studies in rats, dogs, chickens, and rabbits (1-5) show the rapid conversion of ingested nitrofurans to a limited number of structurally related metabolic products, not all of which have been positively identified. However, from work with isotopically labeled nitrofurans, (6) i t is apparent that a consider-

Radioactive impurities known to exist in labeled diethylstilbestrol used in tissue residue studies in cattle include at least five different compounds, one of which is identified as pseudodiethylstilbestrol.