Aging, high salt intake, and renal dopaminergic activity in Fischer 344 rats.
The present study examined renal dopaminergic activity and its response to high salt (HS) intake in adult (6-month-old) and old (24-month-old) Fischer 344 rats. Daily urinary excretion of L-3, 4-dihydroxyphenylalanine (L-DOPA), dopamine, and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid was similar in adult and old rats; by contrast, daily urinary excretion of norepinephrine in old rats was almost twice that in adult animals. HS intake (1% NaCl) over a period of 24 hours resulted in a 2-fold increase in the urinary excretion of dopamine, DOPAC, and norepinephrine in adult animals but not in old animals. Norepinephrine and L-DOPA plasma levels did not change during HS intake and were similar in both groups of rats. The natriuretic response to an HS intake in old rats (from 4.7+/-0.4 to 10.7+/-2.0 nmol. kg(-1). d(-1); Delta=6.0+/-0.9 nmol. kg(-1). d(-1)) was less than in adult rats (from 5.2+/-0.4 to 13.5+/-2.5 nmol. kg(-1). d(-1); Delta=8.3+/-0.8 nmol. kg(-1). d(-1)). A diuretic response to HS intake was observed in adult rats (from 20.9+/-2.3 to 37.6+/-2.8 mL. kg(-1). d(-1)) but not in old rats (from 37.7+/-5.7 to 42.3+/-6. 0 mL. kg(-1). d(-1)). Dopamine levels and dopamine/L-DOPA ratios in the renal cortex of old rats were greater than in adult rats. HS intake increased both dopamine levels and dopamine/L-DOPA ratios in the renal cortex of adult rats but not in old rats. Aromatic L-amino acid decarboxylase activity was higher in old rats than in adult rats; HS intake increased L-amino acid decarboxylase activity (nmol. mg protein(-1). l5 min(-1)) in adult rats (from 67+/-1 to 93+/-1) but not in old rats (from 86+/-2 to 87+/-2). Dopamine inhibited Na(+),K(+)-ATPase activity in proximal tubules obtained from adult rats, but it failed to exert such an inhibitory effect in old rats. It is concluded that renal dopaminergic tonus in old rats is higher than in adult rats but fails to respond to HS intake as observed in adult rats. This may be due in part to the inability of dopamine to inhibit Na(+),K(+)-ATPase activity in old rats.
Vieira-Coelho
M A
MA
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, Houston, Tex 77204-5511, USA.
Hussain
T
T
Kansra
V
V
Serrao
M P
MP
Guimaraes
J T
JT
Pestana
M
M
Soares-Da-Silva
P
P
Lokhandwala
M F
MF
D015102:3,4-Dihydroxyphenylacetic Acid / Q000652:urine; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D002395:Catecholamines / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007980:Levodopa / Q000652:urine; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002395:Catecholamines; D015259:Dopamine Agents; D017673:Sodium Chloride, Dietary; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D008995:Monoamine Oxidase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine