Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess a possible role for endogenous renal dopamine in sodium excretion, the dopa decarboxylase inhibitor carbidopa was given during intravenous salt loading. In addition, the effect of lithium on tubular sodium handling was separately determined. Nine males were studied randomly on three occasions, receiving placebo, lithium carbonate (1000 mg, 11 h prior to study) or carbidopa (100 mg x 2). On each day a baseline period was followed by infusion of isotonic saline (20 ml/kg per hour) over 3 h, and 6 h recovery. With placebo, sodium excretion increased markedly to a peak in the hour after infusion (0.15 +/- 0.03 to 0.73 +/- 0.12 mmol/min, P less than 0.01). Urine dopamine excretion increased modestly (1.33 +/- 0.12 to 1.67 +/- 0.13 mmol/min, P less than 0.01). Carbidopa effectively blocked dopamine output during the study. However, the natriuretic response was comparable to values on placebo at all time points. Fractional lithium clearance, a proposed measure of proximal tubular fluid rejection, increased significantly during saline infusion. However, baseline sodium excretion was greater in the presence of lithium, and plasma renin activity (PRA) was significantly elevated. In addition, the peak natriuretic response was smaller and cumulative sodium excretion reduced by 40% (P less than 0.01) compared to placebo. This study provides no evidence for a facilitatory role for dopamine in the natriuretic response to intravenous salt loading. Lithium, at subtherapeutic levels, cannot be presumed to be an inert marker, and clearance data must be interpreted with caution.
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PMID:The effect of carbidopa and lithium on the systemic and renal response to acute intravenous saline loading in normal man. 252 33

1. The renal response to gamma-L-glutamyl-L-dopa (gludopa, 25 micrograms kg-1 min-1) was investigated in seven normal male volunteers. The effects of oral carbidopa (100 mg) and indomethacin (100 mg) on the response to gludopa were studied in the same group. 2. Gludopa at this dose level produced a 900-fold increase in urine dopamine excretion and caused a natriuresis and suppression of plasma renin activity with only minor effects on pulse rate and blood pressure. 3. Carbidopa inhibited the increase in dopamine excretion by 97% and abolished the renal actions of gludopa. 4. The increase in urine dopamine produced by gludopa was not altered by indomethacin and the urine sodium output was similar to that caused by gludopa alone. 5. Gludopa is an effective renal dopamine prodrug whose activity can be blocked by the dopa decarboxylase inhibitor carbidopa. The results with indomethacin suggest that dopamine and the prostaglandins form separate natriuretic systems in the kidney.
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PMID:The effect of carbidopa and indomethacin on the renal response to gamma-L-glutamyl-L-dopa in normal man. 312 6

1. The urine dopamine response to intravenous frusemide (30 mg) was investigated in 15 salt replete male volunteers. The effects of oral indomethacin (100 mg) and oral carbidopa (100 mg) given before intravenous frusemide were studied in the same group of subjects. 2. Frusemide produced a significant increase in urine dopamine output within 15 min. 3. Indomethacin attenuated the natriuretic and renin responses to frusemide, but did not alter urine dopamine output. 4. Carbidopa lowered urine dopamine to undetectable levels, but did not significantly affect the natriuretic and renin responses to frusemide. 5. We conclude that urine dopamine excretion after frusemide is not directly related to increased sodium excretion or renin response and it is not mediated by the prostaglandins. In addition, dopamine does not contribute to the renal actions of frusemide under normal conditions.
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PMID:The effect of intravenous frusemide on urine dopamine in normal volunteers: studies with indomethacin and carbidopa. 365 22

1. Twelve healthy volunteers maintained on a 100 mmol/day Na+ diet, were given an intravenous infusion of 2L saline (0.9%) between 10.00 h on 2 study days at least 1 week apart. Urine collections (90 min) were made from 08.30 to 16.00 h. Either carbidopa 100 mg or indomethacin 50 mg was given orally at 07.45 h on one study day and placebo was given on the other (in random order). 2. On the placebo day, saline infusion caused significant decreases in plasma albumin concentration, plasma renin activity (PRA), plasma aldosterone concentration and urinary aldosterone excretion, with 2 to 3-fold increases in plasma atrial natriuretic peptide (ANP) concentration and urinary dopamine: noradrenaline ratio (DA:NA), whereas mean urinary kallikrein and prostaglandin E2 (PGE2) excretion rates were unchanged. Carbidopa decreased urinary DA:NA and indomethacin decreased urinary PGE2 excretion, compared with the placebo day. Excretion of sodium (Na+) decreased below baseline in two out of six carbidopa-treated subjects and in three out of six indomethacin-treated subjects, but showed little or no change in the remainder. 3. These preliminary observations suggest that some subjects in the early phase of natriuresis after an intravenous Na+ load can be identified as having prostaglandin-dependent or dopamine-dependent mechanisms for Na+ excretion.
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PMID:Humoral determinants of Na+ excretion after intravenous NaCl loading in normal volunteers. 832 15

1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance. 3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the antinatriuretic effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa. 5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.
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PMID:Comparison of the effects on urinary sodium excretion of indomethacin and of carbidopa in normal volunteers given an intravenous saline infusion. 917 41