1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.
1. To examine the hypothesis that the normalcy of blood pressure, despite an increase in circulating angiotensin II, and the blood pressor hyporesponsiveness to infusion of pressor agents which are associated with hypokalaemia, are due to overproduction of prostacyclin, the principal prostaglandin (PG) synthesized by the vascular endothelium, we studied the effect of experimental hypokalaemia on the urinary excretion of immunoreactive 6-keto-prostaglandin F 1α , a stable metabolite of prostacyclin, in the rat. 2. The animals were fed on a potassium-deficient diet for 9 days. Twenty-four hour urine samples were collected daily for measurement of urinary excretion of immunoreactive 6-keto-PGF 1α , PGE 2 and 13,14-dihydro-15-keto-PGF 2α (PGFM). 3. Hypokalaemia caused significant increases of the three prostaglandins measured. 4. We conclude that hypokalaemia is a potent stimulus of both renal and vascular prostaglandins. The results suggest that an increase in prostacyclin synthesis in peripheral blood vessel walls may be responsible for the resistance of blood pressure to infusion of pressor substances as well as for the normalcy of blood pressure, despite the presence of high circulating angiotensin II concentrations, in conditions associated with hypokalaemia.
1. The response to an infusion of 4% (w/v) fructose in water was determined in fifteen women on a daily sodium intake of 100 mEq/day. The results were compared with those obtained during a similar infusion on another day after treatment with deoxycorticosterone (20 mg/day; seven subjects), or spironolactone (200 mg/day; eight subjects), for 1 day before the day of study. 2. Treatment with deoxycorticosterone significantly ( P < 0·01) decreased sodium excretion (from a mean value of 391 to 192 μEq/min) and urine flow rate (from 14·3 to 12·4 ml min −1 100 ml −1 of glomerular filtrate) without a change in urinary osmolality or the clearance of inulin. The steroid also increased the fractional reabsorption of sodium at the diluting segment of the nephron, but this increase in reabsorption was not sufficient to compensate for the decrease in delivery of sodium to the site, so that absolute free-water clearance decreased. 3. Treatment with spironolactone significantly ( P < 0·01) increased sodium excretion (from 349 to 437 μEq/min) and urine flow rate (from 12·5 to 14·4 ml min −1 100 ml −1 of glomerular filtrate) with essentially no change in urinary osmolality or in inulin clearance. Spironolactone also decreased the fractional reabsorption of sodium at the diluting segment of the nephron, but the degree of inhibition of reabsorption was not sufficient to prevent an increase in free-water clearance as a result of increased delivery of sodium to the site. 4. The findings support the concept that changes in circulating aldosterone can alter the renal excretion of sodium in man by affecting its reabsorption in the proximal tubule as well as in the distal tubule.