Earlier publications questioned the reliability of measurements of renal plasma flow in young infants, since the extraction ratios for para-aminohippurate (EPAH) used were those obtained in adults (1-3). It was suggested that the use of these high values for EPAH to determine renal plasma flow and filtration fraction might not be valid and could account for the high filtration fraction reported in infants under a year of age (1)(2)(3)(4)(5). This high fraction was interpreted to indicate that the rate of glomerular filtration is greater in comparison to renal plasma flow than that in adults. The present study was designed to measure EPAH in young infants in order to arrive at the true value for renal plasma flow and calculated filtration fraction. METHODSFifteen children between 8 days and 10 years old were studied; eight were under 3 months, and seven between 5 months and 10 years old. Pertinent clinical and laboratory data are listed in Tables I through IV. Forty-five minutes before testing, eight of the fifteen patients were given a sedative; ' five were infants (no. 1 and 5-8) and three were older children (no. 10, 11, and 15). Inulin2 and para-aminohippurate (PAH) were administered in normal saline or 5% dextrose in water after base-line control venous blood determinations were made. The diluent and the intervals from the mixing of PAH with the diluent to the end of the test are recorded in Tables II and III. Saline as the diluent for the PAH injection was used in four infants and in two children. Five per cent dextrose in water was the diluent in four infants and in seven children. Two infants and two children were I Chlorpromazine, 6.25 mg per ml; promethazine, 6.25 mg per ml; and meperidine hydrochloride, 25.00 mg per ml. The dose was 1 ml per 20 pounds of body weight, up to a maximum of 2 ml.2 Kindly supplied by the General Diagnostics Division, Warner-Chilcott Laboratories, Morris Plains, N. J. studied with both diluents. All blood samples were collected in heparinized tubes. Inulin and PAH were given to maintain arterial blood concentrations above 25 mg per 100 ml for inulin and below 4 mg per 100 ml for PAH. These values were not always obtained, but in the four infants given PAH in normal saline, the level of renal arterial PAH was over 3.1 mg per 100 ml in only one period of Patient 1. A no. 10 French catheter was placed in the bladder for urine collections. The femoral artery and vein were catheterized with Birds Eye catheters no. 5, 6, or 7. Under direct fluoroscopic supervision, the right renal vein was entered, and an attempt was made to enter the right renal artery; if it was unsuccessful, arterial blood samples were obtained from the aorta close to the renal artery. Spot films were taken to demonstrate the location of catheters before collections were made. Measurements of glomerular filtration rate and effective renal plasma flow measurements were made in three infants and in one older child. Complete emptying of the bladder was obtained by instilling air, and blood was withdrawn simultaneo...
Our laboratory has characterized dopamine receptors in glomeruli and tubular homogenates. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity to dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective, and of high affinity. The apparent dissociation constant was 31.5 X 10(-9) M (+/- 8.5) and the maximum receptor density was 0.31 X 10(-15) M (+/- 0.08) per millimeter. In pars recta specific binding was 53% of total [3H]-haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. Moreover, the stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).
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