In vivo evidence for a defect in the dopamine DA1 receptor in the prehypertensive Dahl salt-sensitive rat.
A defective dopamine DA1 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 DA1 receptor blockade (SCH23390) and of dopamine-synthesis inhibition (benserazide) on volume expansion (VE)-induced sodium and dopamine excretion was studied 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 similarly in the two strains. During peak natriuresis mean arterial blood pressure was 119 +/- 3 and 122 +/- 3 mm Hg, respectively. In DR treated with SCH23390, sodium excretion was only 72% of that in vehicle-treated DR. Dopamine excretion increased, however, as in vehicle-treated DR. In DS, treatment with SCH23390 did not attenuate natriuresis and dopamine excretion also increased as in vehicle-treated DS. In benserazide-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, prehypertensive DR and DS have a similar capacity to acutely excrete an intravenous saline load and to generate dopamine. The total dopamine involvement in VE-induced natriuresis is also comparable in the two strains, but the natriuresis mediated by DA1 receptors is pronounced in DR and non-existent in DS.(ABSTRACT TRUNCATED AT 250 WORDS)
Hansell
P
P
Department of Physiology and Medical Biophysics, University of Uppsala, Sweden.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000652:urine
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D001545:Benserazide; D012964:Sodium; D004298:Dopamine