The work outlined in the following pages was devoted to studying the source of urinary dopamine (DA) as well as the position of DA within the natriuretic system. First, the availability of catecholamines (CA) in some peripheral tissues and plasma of normotensive and hypertensive rats was assessed. Following their estimation using high performance liquid chromatography with electrochemical detection (HPLC-EC), noradrenaline (NA), adrenaline (ADR), and dopamine (DA) were abundant in the rat heart, adrenals, kidneys, and to a much lesser extent in the plasma. In addition, the effect of species, sex, and mode of sacrifice were studied. None of these factors affected the levels of CA in the kidney. From this experiment, it was concluded that tissue concentration may not be the ideal parameter to study, especially when analysing the effect of the mode of sacrificing the experimental animals. Amine turnover may provide a more reliable measure.;The concentration of these CA were studied in plasma, heart, kidney and adrenals taken from normotensive and spontaneously hypertensive rats (SHR). With the exception of cardiac NA, and to a much lesser extent adrenal DA, no significant difference was seen. The reduction of cardiac NA was attributed to the increased release of NA coupled with low turnover of the amine in SHR. Moreover, expressing the levels of these amines in relation to tissue protein content did not alter the significance already seen when CA were expressed in relation to the weight of the tissues used, indicating that oedema formation had not influenced the levels of CA observed in SHR.;In rats administered 3% solutions of either NaCl, CaCl2 or NaHCO3 for a period of 3 days, the levels of CA in the kidney and plasma and, to a lesser extent, in the adrenals were unchanged. A greater effect of this treatment was observed on the concentration in hearts loaded with CaCl2. This effect seems to be due to the known effect of Ca++ on the cardiac muscle. The results of all these experiments indicated that a continuous turnover takes place in the tissues studied, thus masking any alterations due to salt loading or changes in species, sex, or mode of sacrifice.;The high levels of urinary DA estimated in the last experiments, taken with the low plasma levels of the amine stimulated the search for a possible source of urinary DA. The study involved the role of the adrenal gland and the sympathetic neurons and was carried out in adrenalectomized rats and in rats dosed with 6-OHDA.;The relationship between DA and Na+ was studied in rats infused with different concentrations of salts. The infusion of hypotonic solution resulted in a reduction in Na+ and DA excretion, while hypertonic saline did not affect DA, but Na+ excretion was greatly enhanced. The effect of hypotonic saline was attributed to an increased proximal tubular reabsorption of Na+ while that of hypertonic saline was probably due to a multiple action of suppressing aldosterone secretion and enhancing the release of a natriuretic substance.;Finally, a correlation was observed between urinary DA excretion and that of Na+, while no correlation was found between DA and Cl- excretion, indicating the importance of Na+ and the possible participation of DA as a member of the natriuretic cascade.;Therefore, the main conclusions from this work are that the adrenal gland contributes about 44% to urinary DA while the sympathetic nervous system contributes no more than 20%. This huge amount of DA appearing in the urine seems to be related directly to urinary excretion of Na+ ion thus suggesting this endogenous DA to qualify as a natriuretic hormone within the natriuretic system. (Abstract shortened by UMI.).
|Date of Award||1985|