Effects of carbidopa and of intravenous saline infusion into normal and hypertensive subjects on urinary free and conjugated dopamine.

OBJECTIVE: To investigate the possible role played by endogenous dopamine as a modulator of renal sodium (Na+) reabsorption after a combined Na+ and volume load. DESIGN: A randomized placebo-controlled study. METHODS: Ten healthy volunteers and four hypertensive patients were subjected to intravenous infusions of 21 0.9% saline (308 mmol Na+) administered from 1000 to 1300 h after oral administration of placebo or of carbidopa, a dopamine decarboxylase inhibitor. RESULTS: Studies on control subjects after placebo showed that natriuresis occurred during the 6 h after commencement of the saline infusion, with falls in plasma albumin concentration, plasma renin activity and plasma aldosterone concentration; in comparison with results of mock infusion (6 mmol Na+) there was no change in the urinary excretion of dopamine and noradrenaline (In their free or conjugated forms). There was, however, a marked surge in excretion of urinary conjugated dopamine and in the dopamine: noradrenaline ratio from 1300 to 1600 h, after either type of infusion. Administration of carbidopa before the saline infusion resulted in a marked decrease in excretion of urinary free dopamine, but had no effect on the surge in excretion of urinary conjugated dopamine. Saline infusion decreased proximal fractional Na+ reabsorption. Administration of carbidopa delayed but did not prevent this decrease. The effects of saline infusion and of carbidopa on the urinary excretion of dopamine and noradrenaline from hypertensive patients were similar to those observed with the healthy volunteers. CONCLUSIONS: These findings indicate that volume expansion by intravenous saline infusion has no appreciable effect on the urinary free dopamine excretion from normal or hypertensive humans; with any apparent increase, it is important to exclude the possibility of conversion of conjugates to free dopamine in vitro. Furthermore, that carbidopa administration did not inhibit the afternoon surge of conjugated dopamine suggests that administration of carbidopa is deficient as a tool to investigate the functional role of the renal dopamine system.

Comparison of the effects on urinary sodium excretion of indomethacin and of carbidopa in normal volunteers given an intravenous saline infusion.

1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance. 3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the antinatriuretic effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa. 5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.

Quality assurance for biogenic amines with authentic patient specimens.

The measurement of biogenic amines and metabolites is essential for diagnosis and follow-up of neural crest tumors. A Quality Assurance programme involving the distribution of urine specimens obtained from patients with neural crest and related tumors was conducted by the Australian Association of Clinical Biochemists' Working Party on Biogenic Amines in 1988. Fifty laboratories participated in the programme and measured a number of analytes with a variety of methods. These included high performance liquid chromatography with electrochemical detection (HPLC-EC), spectrophotometry, fluorescence, fluorescence polarization immunoassay (Abbott TDX) and gas chromatography--mass spectroscopy (GC-MS). The results of this survey indicated that fluorimetric methods for catecholamines are unreliable as they are subject to interference particularly by Labetalol. Twice as many laboratories utilized catecholamines rather than metanephrines for detection of pheochromocytoma. 5-HIAA appears to be the analyte measured with the least accuracy, particularly with spectrophotometric methods of analysis. Several laboratories would have failed to diagnose some neural crest tumors and need to improve their performance.

Analysis of barbiturates by gas chromatography.

This review surveys the evolution of gas chromatographic procedures for the quantification of barbiturates as either the free acids or their derivatives obtained by direct and on-column reactions. Among the aspects discussed, some emphasis is placed on recognized and other sources of interference encountered during analyses.

Relative electron capture response of the 2-chloroethyl derivatives of some barbituric acids and anticonvulsant drugs.

Data are given for the relative electron capture response of the 2-chloroethyl derivatives of ten barbituric acids and five common anticonvulsant drugs. Results indicate that these new derivatives significantly improve the detection limits of the barbituric acids but lead to no advantages for the anticonvulsant compounds. Structural features in the two classes of compounds are believed to explain the differences in the sensitivity of detection. Linear calibration plots exist for the concentration ranges 0.1-1.0 and 1.0-10.0 microgram/ml of amobarbital.