John M. Weller

Effect of an Intravenous Sodium Chloride Load on Renal Hemodynamics and Electrolyte Excretion in Essential Hypertension

Excretion of infused sodium, chloride, and water increased proportionately in patients with progressively more severe grades of hypertension and of increased renal vascular resistance. These relationships held so long as renal plasma flow and glomerular filtration rate were not greatly impaired. The abnormality was characterized by increased renal tubular rejection of sodium, chloride and water.

Sodium Chloride Excretion Following Salt Loading in Hypertensive Subjects

Patients with essential hypertension show an altered renal excretory response to sodium chloride loading. Hypertensive patients acutely eliminate a greater proportion of a salt and water load than do normotensive subjects. This renal abnormality appears to be due to an augmented tubular rejection of sodium chloride and water. This study further defines the nature and extent of this alteration in electrolyte and water metabolism.

Effect of minoxidil on blood pressure and hemodynamics in severe hypertension

Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.

Potentiation of gentamicin nephrotoxicity by metabolic acidosis.

Summary Gentamicin nephrotoxicity was examined in normal rats and in rats chronically ingesting 1% NH4C1 solution. Metabolic acidosis significantly exacerbated gentamicin nephrotoxicity as manifested by elevation of SUN and depression of tissue uptake of PAH and TEA by renal cortical slices. In contrast normal rats given the same dose of gentamicin did not develop nephrotoxicity. Pathological examination confirmed that acute tubular necrosis occurred only in the acid-loaded rats injected with gentamicin.

Effects of benzothiadiazine drugs on carbohydrate metabolism

Abstract The administration of chlorothiazide both to man and to rats results in hyperglycemia following a glucose load. Its administration to rats causes a decreased rate of glucose utilization by their adipose tissue in vitro. Chlorothiazide added directly to the incubating medium also decreases the rate of glucose utilization of rat adipose tissue. These effects of chlorothiazide are most likely due to both a direct action of the drug on tissue glucose metabolism and an indirect effect which is the result of chlorothiazide causing a decrease in the level of serum insulin-like activity which in turn diminishes the activity of insulin-dependent enzymes involved in glucose metabolism.

Renal Hemodynamics in HgCl2-Induced Acute Renal Failure

Renal blood flow (RBF), outer cortical blood flow (OC-rbf) and inner cortical blood flow were determined by the microsphere method in water-drinking rats and chronic saline-drinking rats at 3, 12 and 24 h after injection of HgCl2, 4.7 mg/kh body weight. RFB and OC-rbf were decreased in both groups at 3 h post HgCl2 injection. Persistent reduction of OC-rbf was noted in water-drinking rats at 12 and 24 h post HgCl2 even though the total RBF returned to normal by 24 h. These parameters were normal in chronic saline-drinking rats. Despite normal RBF in water-drinking and saline-drinking rats, serum creatinines were still signigicantly elevated 24 h post HgCl2. Therefore, alterations in total renal perfusion do not entirely account for the decreased renal function that occurs under these circumstances.

Effect of Nandrolone Decanoate on the Anemia of Chronic Hemodialysis Patients

A double-blind cross-over study was conducted on 21 patients on maintenance hemodialysis to determine if changes in serum erythropoietin level, packed cell volume, red cell mass, hemoglobin concentrat

In vitro uptake of gentamicin by rat renal cortical tissue.

The mechanism of gentamicin uptake in vitro by renal cortical slices of rat kidney was investigated. The cortical-slice-uptake ratio of gentamicin concentration in 1.0 g of tissue water to that of 1.0 ml of incubation medium (SW/M) was 1.44 ± 0.04. The uptake of gentamicin was inhibited by 2 × 10−5 M dinitrophenol (SW/M = 1.03 ± 0.04) and by anoxia (SW/M = 1.01 ± 0.04). The results indicate that aerobic phosphorylation is required to transport gentamicin into the cells. The uptake of p-aminohippurate and tetraethylammonium chloride by renal cortical slices was not affected by gentamicin.

Influence of Race of Cadaveric Kidney Donor and Recipient on Graft Survival: A Multifactorial Analysis

Actuarial survival analysis of 889 cadaver transplant patients between 1972 and 1981 in Michigan reveals functional graft (P = .0003) and patient (P = .004) survivals are improved when donors and recipients are of the same race (black or white). The Cox regression model for multifactorial analysis confirms the significantly lower graft survival for the mixed racial combination group with a relative risk of 1.27 (P less than .05). By this analysis, other significant factors adversely affecting the graft survival rates include diabetes as a cause of end-stage renal disease, earlier date of transplantation, shorter duration of prior dialysis, and a significant center effect. Patient survival has a significantly greater relative risk for the black to white racial combination, diabetes, earlier calendar year of transplantation, and age of patient. While the mixed racial group was slightly older (delta = 2 years), had more hypertension, less glomerulonephritis, and more HLA mismatches, our analysis by the Cox regression model suggests that these factors played only minor roles (P greater than .05) regarding graft survival rates. Therefore, our data suggest that independent of several other factors, cadaver kidneys have a better functional outcome when they are transplanted into recipients of the same race.

Measurement of Renal Blood Flow in the Rat

A radioactive microsphere technique has been developed for the measurement of renal blood flow and intrarenal blood flow distribution in the dog (1, 2). Various techniques have been proposed (3-5) for the measurement of renal blood flow (RBF) in the rat in addition to the conventional PAH clearance method. This study presents a simple method for the assessment of RBF in rats using radioactive microspheres. Method. Eight male Sprague-Dawley rats weighing 200-240 g were fed with Purina Lab Chow and given tap water ad lib. All animals were lightly anesthetized with ether and cannulated with polyethylene tube No. 10 (i.d. 0.011 in., o.d. 0.024 in.) through the femoral artery for blood collection and through the carotid artery into the left ventricle for injection of microspheres. After awakening from anesthesia, animals were placed in restraining cages and allowed to recover for 45-60 min prior to injection. Radioactive microspheres, 15 μm ± 5 μm diameter, (3m Co., St. Paul, MN) were utilized to measure renal blood flow (RBF) and its intracortical distribution. Two different nuclides were used, 85Sr and 141Ce, for two separate measurements taken 1 hr apart. For each measurement, approximately 0.1 ml of 2 mg/ml concentration of microspheres in 10% dextran was injected through the carotid artery catheter within 5-7 sec. Just prior to injection, the spheres were sonicated for 5-10 min and then vigorously agitated with a vortex mixer for at least 3 min. Immediately upon injection of the spheres into the left ventricle, the femoral catheter was opened and blood was allowed to flow freely into a preweighed tube for exactly 1 min. Approximately 0.2 ml of blood was collected from the femoral artery in each minute. The adequacy of 1-min collection periods, vis à vis complete removal of microspheres from the circulation, was tested in a separate group of five animals.