The effect of carbidopa and indomethacin on the renal response to gamma‐ L‐glutamyl‐L‐dopa in normal man.

Abstract

1 The renal response to y-L-glutamyl-L-dopa (gludopa, 25 ,ug kg-1 min-') 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.

Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension.

“…The increased blood pressure is associated with increased renal renin activity. Dopamine and dopaminergic drugs have been reported to increase renin secretion in some studies and to decrease it in other studies (8,(11)(12)(13). These apparently conflicting reports can now be explained by the contrasting effects on renin secretion after stimulation of dopamine receptor subtypes.…”

“…The other D 1 -like receptor, the D 1B receptor, is not expressed in rat juxtaglomerular cells (8). D 2 -like receptors probably mediate the inhibitory effect of dopamine on renin secretion (11)(12)(13). Since D 3 but not D 2 receptors are present in rat juxtaglomerular cells and since D 3 receptor stimulation inhibits cAMP accumulation in these cells, we have suggested that the D 3 receptor may be responsible for the dopamine-mediated decrease in renin secretion in these cells (14,15).…”

“…Thus, an abnormality resulting in inhibition of a D 1 -like receptor function may lead to sodium retention and simultaneously produce a low renin state (10). In contrast, D 2 -like receptors have been shown to inhibit renin release (11)(12)(13). The D 2 -like receptor that negatively regulates renin secretion may be the D 3 receptor since it is expressed in juxtaglomerular cells while the D 2Long receptor is not (14).…”

(+)‐sulpiride antagonises the renal effects of gamma‐L‐glutamyl‐L‐dopa in man.

“…We have recently shown that effects of gludopa are abolished by prior treatment with carbidopa (Jeffrey et al, 1988) which prevents conversion of gludopa to dopamine. Glutyrosine, which is structurally similar to gludopa does not increase urine dopamine and is not natriuretic providing evidence against a non specific effect of gludopa.…”

Mild exercise activates renal dopamine system in mild hypertensives

“…If urinary DA is formed from the uptake of circulating DOPA and is decarboxylated in the kidney, then inhibition of L-AAAD should decrease urinary DA excretion, as has actually been reported. [40][41][42] DA is known to suppress Na + , K + -ATPase activity in the proximal convoluted tubule (PCT) and the thick ascending limb of the loop of Henle. 43 The Na + , K + -ATPase is located mainly on the basolateral membranes, where the stimulatory effect of DA on phospholipase C predominates, resulting in activation of protein kinase C and inhibition of Na + , K + -ATPase activity.…”