It has been postulated that endogenously produced dopamine (DA) may play a role in the regulation of renal sodium excretion. In the present study, experiments were designed to test the hypothesis that acute volume expansion with isotonic sodium chloride stimulates the production of DA within the kidney, which in turn acts on specific DA, receptors to promote sodium excretion. In pentobarbital-anesthetized rats, acute volume expansion over a period of 1 hour evoked a pronounced increase in urine output and urinary sodium excretion. These diuretic and natriuretic effects were not accompanied by any significant changes in blood pressure or heart rate. However, there was a significant elevation in central venous pressure and a transient rise in glomerular filtration rate. The natriuretic and diuretic response was accompanied by a significant increase in urinary DA excretion, and this effect was clearly dissociated from the rise in glomerular filtration rate. In a separate group of rats, the effects of acute volume expansion were studied in the presence of selective DA, receptor antagonist SCH-23390 (50 figlkg i.v. bolus; 10 /xg/kg/min). During DA, receptor blockade, there was a marked attenuation in the diuretic and natriuretic response throughout the period of volume expansion, when compared with that in the control group. The changes in central venous pressure and glomerular filtration rate were identical in the two groups. In another group of rats, the renal effects of exogenously administered DA were studied. DA (0.5 /ug/kg/min) produced significant increases in urine output and urinary sodium excretion, without causing any alterations in blood pressure or glomerular filtration rate, suggesting a tubular site of action. SCH-23390, in a dose that had previously attenuated the natriuretic response to volume expansion, blocked the diuretic response and attenuated the natriuretic response to DA. The DA, receptor antagonist produced no significant hemodynamic and renal effects by itself in normally hydrated animals. These results suggest that endogenously produced DA contributes, at least in part, to the natriuretic and diuretic response to acute volume expansion by activation of DA, receptors located on renal tubules. (Hypertension 1989;13:828-834) D opamine (DA) has the ability to produce a variety of cardiovascular and renal effects by acting on specific DA receptors. 1 The renal effects of DA include increases in glomerular filtration rate and renal blood flow as well as diuresis and natriuresis.2 DA receptors of both the DA, and DA 2 subtype have been identified in the nephron using radioligand binding techniques.3 -5 In addition, DA has been shown to produce an inhibition of Na + ,K + -ATPase in the proximal tubule, a potential mechanism to explain its natriuretic effect.

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Activation of phospholipase C (PLC) is considered to be one of the cellular signaling events involved in dopamine (DA)-mediated natriuresis. In the present study we have examined the role of renal cortical PLC in contributing to the increase in urinary sodium excretion during high sodium intake and its relationship with intrarenal DA synthesis. Rats were given either 1% NaCl (high sodium intake) or tap water (normal sodium intake) to drink for 24 h, and urine was collected over this time period. PLC activity in the renal cortex from these rats was measured by prelabeling cortical slices with myo-[2-3H]inositol and was expressed as fractional release (FR) of inositol (mono-, bis-, and tris-) phosphates. Acute increase in sodium intake produced 93 +/- 8% increase over control in urinary DA excretion. These changes were accompanied by significant increases (30 +/- 8%) in basal FR of inositol phosphates and 243 +/- 40 and 76 +/- 14% increases in urinary sodium and water excretion, respectively. The elevated basal PLC activity in rats with high sodium intake was significantly reduced in the presence of Sch 23390, a selective DA-1 receptor antagonist. Exogenously added DA (3 mM) also produced significant increases in PLC activity, although the magnitudes of increases were different in rats with high (37 +/- 8%) and normal (66 +/- 9%) sodium intake. However, Sch 23390 alone or carbidopa pretreatment did not affect the basal PLC activity in rats maintained on normal sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)

The basal and K+‐induced release of dopamine and its metabolites, 3,4‐dihydroxyphenylacetic acid and homovanillic acid, were measured in microdialysate samples obtained in vivo from the nucleus accumbens region of rats subchronically exposed to 50 ppm lead for 90 days. The basal and stimulus‐induced release of dopamine and the metabolites were significantly reduced in the lead‐exposed rats as compared with the controls. These reductions in dopamine and its metabolites are consistent with the reports of decreased dopamine availability associated with lead‐induced changes in certain behavioral indices (fixed‐interval performance) in rats. Furthermore, these changes were observed at blood lead levels similar to those considered to cause impairment in cognitive functions in children.

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