Differences in the renal dopaminergic system between a salt-resistant and a salt-sensitive strain of rat

Defects in the renal dopaminergic system have been implicated in the aetiology of some forms of salt-sensitive hypertension. The present study investigated this system in two genetically related strains of rag the salt-resistant Long Evens (LE) and the salt-sensitive Brattleboro Normal (BBN) rat. The urinary dopamine output and renal cortical L-aromatic amino acid decarboxylase (L-AAAD) of LE and BBN rats were measured on low and normal salt diets. The dopamine output fell in LE rats when dietary sodium was increased, whilst it did not change significantly in the BBN rats. L-AAAD from LE mts showed a decreased affinity for its substrate L-DOPA when dietary sodium was increased, whilst the V-max was unchanged Neither parameter changed in the BBN rats. The basal V-max of BBN rats was over twice as high as LE rats, while the dopamine excretion rates were similar. This suggests an inhibitory mechanism present in the BBN rats that is absent from LE rats. This may contribute to the observed salt-sensitivity of the BBN strain. Renal DA(1) receptors identified using [H-3]SCH23390 in renal cortical membranes from BBN rats showed a high affinity and a low affinity binding site. Only the low affinity site could be identified in the LE rats. Dopamine, and the DA(1) agonist fenoldopam, stimulated the production of cAMP by renal cortical membranes from BBN rats in a concentration-dependent manner but had no effect on membranes from LE rats. This inability may be related to the lack of high affinity DA(1) binding site in this strain. These differences may reflect alterations in the dopaminergic regulation of sodium excretion in these two closely related strains of rat.