Dopamine D-3 receptors and salt-dependent hypertension

Alterations in the dopaminergic system may contribute to the pathogenesis o f hypertension. Dopamine D-3 receptors have been shown to be involved in th e regulation of sodium balance and hemodynamics in rodents. For determining the role of D-3 receptors in salt-dependent hypertension, clearance experi ments were performed in anesthetized salt-sensitive (DS) and salt-resistant (DR) Dahl rats that were fed a standard diet with either normal (0.2%) or high (4%) sodium content for 21 to 26 d, which induced hypertension in DS b ut not in DR rats. The D-3 receptor agonist R(+)-7-hydroxydipropyl-aminotet ralin (7-OH-DPAT) increased GFR by up to 35% and urinary sodium excretion b y up to 4.4-fold in DR rats that were on both normal and high-sodium diet. 7-OH-DPAT-induced natriuresis also was observed in DS rats that were on nor mal diet but not in hypertensive DS rats that were on high-salt diet. No GF R response to 7-OH-DPAT was found in DS rats, irrespective of sodium diet. The diminished functional response to D-3 receptor stimulation in DS rats w as associated with a significantly lower [H-3]-7-OH-DPAT binding to renal m embrane protein when comparing DS with DR rats. Consequently, DR rats were treated with BSF 135170, a novel, highly selective D-3 receptor antagonist, for 29 d. Whereas no change in systolic BP was observed during normal diet , high sodium intake significantly increased BP by almost 40 mmHg. In summa ry, both expression and function of the renal dopamine D-3 receptor are imp aired in salt-sensitive Dahl rats. Together with the induction of salt-depe ndent hypertension in genetically salt-resistant Dahl rats by D-3 receptor blockade, the data strongly suggest that the deficiency in dopiamine D-3 re ceptors represents an important pathophysiological factor in the developmen t or salt-dependent hypertension.