Renal dopamine and autocrineparacrine function

During the past decade dopamine has been shown to be an active modulator of sodium balance, by actions in the adrenal gland (27,28), intestinal (29-31) and renal epithelia (11,14-26,33-82), and sympathetic nervous system (83). Although the dopaminergic system is active in various anatomic locations, the concentrations of dopamine found circulating in the blood (picomolar) are not high enough to activate the dopamine receptor because nanomolar concentrations are required for receptor activation. However, high nanomolar concentrations of dopamine can be generated locally by the conversion of L-DOPA found in the circulation to dopamine by L-aromatic amino acid decarboxlase found in dopamine-producing tissues (e.g., renal proximal tubule and jejunum). In the proximal tubule, dopamine does not become converted to norepinephrine (as in neurons) because renal tubules do not express dopamine ^-hydroxylase. Dopamine produced intracellularly is then secreted into the tubular lumen, to a greater extent than in the peritubular areas, in which it acts as an autocrine/paracrine hormone to regulate sodium and chloride transport in the renal proximal tubule, thick ascending limb of Henle, and cortical collecting duct.

Long-term sodium (and chloride) balance during moderate sodium surfeit is regulated by locally generated dopamine, which acts on renal tubular and jejunal cells to decrease sodium transport. The dopaminergic renal control mechanism has a major impact on overall sodium balance because over 50% of incremental sodium excretion that occurs with increased sodium intake is regulated by dopamine receptors (39,41,74,77,78,84). Renal hemodynamic mechanisms contribute to the increase in sodium excretion associated with protein loading (171). However, the paracrine/autocrine dopaminergic regulation of sodium excretion during sodium surfeit is mediated by tubular but not by hemodynamic mechanisms (42,74). Systemically administered dopaminergic drugs increase sodium excretion by both hemodynamic and tubular mechanisms. The clinical practice of systemically administering dopaminergic drugs during shock may not mimic the autocrine/paracrine function of dopamine because high doses of dopamine result in concentrations that can activate nondopaminergic receptors, such as the serotonin, a and P adrenergic receptors.

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