Chronic manipulation of dietary salt modulates renal physiology and kidney dopamine receptor subtypes: functional and autoradiographic studies.
1. Compared to rats maintained on the normal NaCl (0.33%) diet, animals maintained on the low NaCl (0%) diet for 4 weeks exhibited increased plasma aldosterone and chloride and decreased urinary sodium excretion. 2. Rats maintained on the high NaCl (8%) diet for 4 weeks showed increased systolic blood pressure, water intake, urine volume, sodium and dopamine excretion and decreased plasma aldosterone and glomerular filtration rate. 3. Administration of SCH 23390 (10 mg/kg, po), but not domperidone to the high salt diet rats attenuated the diuretic effect, indicating the involvement of DA1 rather than DA2 receptors. The dopamine decarboxylase inhibitor, carbidopa (30 mg/kg, i.p.), also reduced the high salt-induced diuresis. 4. Kidney sections from rats fed the low NaCl diet showed a 63-100% decrease (P < 0.001-0.02) in cortical and medullary DA1 and DA2 binding sites, while rats fed the high NaCl diet demonstrated only a 70% decrease (P < 0.01-0.02) in cortical DA1 binding, without affecting DA2 binding. 5. These data indicate that chronic modification of dietary salt profoundly affects the sodium, water and dopamine excretion and leads to selective modulation of renal dopamine receptor subtypes.
Sharif
N A
NA
Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94303, USA.
Nunes
J L
JL
Lake
K D
KD
McClelland
D L
DL
Corkins
S F
SF
Lakatos
I
I
Rosenkranz
R P
RP
Whiting
R L
RL
Eglen
R M
RM
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D004032:Diet; D004231:Diuresis / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012982:Sodium, Dietary; D004294:Domperidone; D002230:Carbidopa