Neural factors in the development of renal function: effect of neonatal central catecholaminergic lesions with 6-hydroxydopamine.
Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of their target tissues. In the current study, we investigated the role of sympathetic tone in the functional development of the kidney in rats, using neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA). This treatment destroys central catecholaminergic pathways and permanently reduces sympathetic activity without ablating peripheral nerve terminals. Renal function was evaluated over the first two postnatal weeks, when glomerular and tubular function undergo rapid development. Although basal renal clearance and the homeostatic response to fluid deprivation developed normally in the lesioned rats, the response to a maximally-effective dose of desmopressin acetate (DDAVP), a vasopressin analog, became deficient by the end of the second week. After weaning, the lesioned animals were unable to survive a chronic salt load, which requires sustained water reabsorption but high output of sodium. These data indicate that normal sympathetic tone is required for appropriate development of the responsiveness of the renal tubule to vasopressin.
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
J A
JA
Gray
R J
RJ
Kavlock
F J
FJ
Seidler
T A
TA
Slotkin
D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000254:growth & development* / Q000294:innervation / Q000502:physiology; D008297:Male; D018377:Neurotransmitter Agents / Q000502:physiology; D016627:Oxidopamine / Q000008:administration & dosage; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D018377:Neurotransmitter Agents; D016627:Oxidopamine; D003894:Deamino Arginine Vasopressin