Cyclosporin A (CsA) is widely used to suppress graft rejection following transplantation and in the treatment of a variety of autoimmune diseases. Therapy with CsA is often accompanied by adverse effects which include hepatotoxicity, hypertension, and nephrotoxicity. The role of endothelin (Et) in CsA-induced nephrotoxicity has been the subject of recent investigations. BQ-123 is a recently discovered Et receptor antagonist which is selective for the EtA receptor. In the present study, BQ-123 was used to further characterize the role of Et in CsA-induced nephrotoxicity. All experiments were performed in Inactin (100 mg/kg, i.p.) anesthetized male Munich-Wistar rats (250 to 350 g). Animals were prepared for the recording of blood pressure (MAP) and heart rate (HR) as well as the measurement of urine volume (UV), UNaV, UKV, GFR and effective renal plasma flow (ERPF). GFR and ERPF were estimated from the clearance of 14C-inulin and 3H-PAH, respectively. On the day of the experiment, animals were randomly assigned to one of three groups and treated according to the following protocols: Group 1, pretreatment with BQ-123 (1 mg/kg, i.v. bolus with 0.1 mg/kg/hr i.v. infusion) followed by treatment with vehicle (cremophor; 0.15 ml, i.v.); Group 2, pretreatment with normal saline (1.0 ml/kg; plus 25 microliters/min infusion) followed by treatment with CsA (20 mg/kg, i.v.); and Group 3, pretreatment with BQ-123 (same as group 1) followed by CsA (20 mg/kg, i.v.). BQ-123 administration alone produced transient changes in several of the measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of defined increments of weight loss on hemodynamics has been investigated in conscious, unrestrained, spontaneously obese rats. Obese rats were subjected to a calorically restricted diet and were used for experimentation on achieving a 10, 20, or 30% reduction in body weight. After monitoring resting blood pressure and heart rate, radioactive microspheres were infused for determination of blood flow distribution. Of 10 organs sample, only heart, liver, kidneys, and 2 adipose tissue depots exhibited significant decreases in weight associated with body weight reduction. Mean arterial blood pressure remained unchanged, while stroke volume, left ventricular work, and cardiac output decreased significantly. Blood flow decreased to kidneys, testes, and adipose tissue through a 30% reduction in body weight, but the fractional distribution of cardiac output decreased only to adipose tissue. Therefore the large decreases in renal and adipose tissue blood flow during weight reduction may contribute to the associated decrease in cardiac output. Of those vascular beds examined, however, both absolute and relative blood flow decreased only to adipose tissue, thus denoting the influence of fat mass on hemodynamics during obesity.

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The standard method for water clarification in SAGD operations involved the injection of latex polymers to break produced reverse emulsions. Operationally, this resulted in large quantities of oil in the water downstream of the first oil and water separation vessel. Problems occurred because this generated large amounts of oily solids and emulsion. This slop material represented a significant additional expenditure. Champion developed a novel approach to treat these systems and reduce slop. This program has been very successful in removing oil from the water stream during primary separation, thus reducing costs associated with reprocessing slop oil, and resulting in greater oil recovery.