Date of Award
Doctor of Philosophy in Pharmaceutical Sciences
David R. DeFanti
The possible relationship among urinary dopamine levels, circulating dopamine levels, kidney dopamine levels and arterial blood pressure was studied in hypertensive rats and dogs. The role of the kidney in the formation of dopamine from dihydroxyphenylalanine (DOPA) was also investigated in cats.
Hypertension was produced by right renal nephrectomy followed in two weeks by contralateral renal artery compression.
The blood pressure of both the rats and dogs showed a sharp increase the first week following the second operation and remained elevated for the duration of the study. Individual pressures as high as 205 mm Hg were encountered.
Dopamine was extracted from urine by absorption onto alumina, converted to its trihydroxyindole derivative and measured fluorimetrically. Tissue and blood samples were for the most part homogenized in trichloroacetic acid, then passed through alumina columns. Dopamine was separated from DOPA by passing trichloroacetic acid extracts through columns of sodium Dowex 50W-X8 to extract dopamine, then through alumina columns to extract DOPA.
Urinary dopamine levels were reported as micrograms per liter (μg/l), micrograms per 24 hours μg/24h) and micrograms per killogram per 24 hours (μg/kg/24h). In comparisons with a control group, the dopamine levels (μg/l) were significantly lower in the hypertensive group on several occasions, however dopamine levels expressed as μg/24h or μg/kg/24h differed only on two occasions; once prior to any operational procedures and then the first week following renal artery compression. A diuresis was observed in the hypertensive animals which could account f or the decrease in urinary dopamine concentration (μg/l) which was obtained. Over the duration of the rat study, mean dopamine levels (μg/l) remained relatively constant and varied between 168 and 418 μg/l, paired mean dopamine levels (μg/24h) showed a tendency to rise and varied between 4.61 and 10.80 μg/24h and mean dopamine levels (μg/kg/24h) showed a slight tendency to decrease, ranging from 11.51 to 18.53 μg/kg/24h.
Correlation and regression analyses for the dependency of arterial blood pressure on urinary dopamine levels (μg/l, μg/24h and μg/kg/24h). did not detect any statistically significant relationships. No significant relationship was established between' dopamine levels (μg/kg/24h) and weight (gm).
Dopamine could not be detected in the blood of hypertensive rats or dogs, or in the ischemic kidneys of hypertensive rats.
The infusion of DOPA into cats with and without functional renal tissue produced similar tissue dopamine levels in the liver, heart and spleen, However, renal arterio-venous differences showed that some DOPA was decarboxylated to dopamine in the kidney.
No evidence was obtained in the study which implicated dopamine in the hypertensive process and no relationship between arterial blood pressure and urinary or circulating dopamine was established.
Coates, David William, "The Relationship of Dopamine to Blood Pressure in Experimental Renal Hypertension" (1968). Open Access Dissertations. Paper 143.