IN-VIVO EVIDENCE FOR A DEFECT IN THE DOPAMINE DA(1) RECEPTOR IN THE PREHYPERTENSIVE DAHL SALT-SENSITIVE RAT

A defective dopamine DA(1) receptor has been suggested to be involved in the salt-sensitive hypertension in Dahl-S rats (DS). To investigate the consequences of this defect, the influence of DA(1) receptor bloc kade (SCH23390) and of dopamine-synthesis inhibition (benserazide) on volume expansion (VE)-induced sodium and dopamine excretion was studie d in anesthetized prehypertensive DS and salt-resistant Dahl rats (DR) . Under control conditions all measured variables were equal in DR and DS. During VE (5% of BW), sodium and dopamine excretion increased sim ilarly in the two strains. During peak natriuresis mean arterial blood pressure was 119 +/- 3 and 122 +/- 3 mm Hg, respectively. In DR treat ed with SCH23390, sodium excretion was only 72% of that in vehicle-tre ated DR. Dopamine excretion increased, however? as in vehicle-treated DR. In DS, treatment with SCH23390 did not attenuate natriuresis and d opamine excretion also increased as in vehicle-treated DS. In benseraz ide-pretreated DR and DS, sodium excretion during VE was similar, but only 50-51% of that in the respective vehicle-treated group. Dopamine excretion decreased by about 80% in both strains. In conclusion, prehy pertensive DR and DS have a similar capacity to acutely excrete an int ravenous saline load and to generate dopamine. The total dopamine invo lvement in VE-induced natriuresis is also comparable in the two strain s, but the natriuresis mediated by DA(1) receptors is pronounced in DR and nonexistent in DS. The study gives in vivo support to the previou s in vitro finding of a defect in the DA(1) receptor in DS; however, t he ability of DS to excrete an acute saline load is not impaired sugge sting that other systems involved in sodium homeostasis compensate for the defect in this strain.