Do sympathetic neurons coordinate cellular development in the heart and kidney? Effects of neonatal central and peripheral catecholaminergic lesions on cardiac and renal nucleic acids and proteins.
Sympathetic nerve activity has been hypothesized to set the timing of cellular maturational events in target tissues. In the current study, this hypothesis was tested by lesioning catecholamine pathways in the periphery and central nervous system through the use of subcutaneous or intracisternal injections of 6-hydroxydopamine. Systemically administered 6-hydroxydopamine completely depleted peripheral norepinephrine. The central treatment completely ablated the developmental rise in brain norepinephrine and dopamine and had little effect on peripheral norepinephrine levels, but has been shown to reduce sympathetic tone. In both the heart and the kidney, either type of lesion resulted in deficits in cell acquisition (DNA) with some evidence of compensatory increases in other macromolecules involved in cell enlargement (particularly RNA), thus maintaining the tissue growth rate at only slightly subnormal levels. The peak effect was always seen during the stages at which sympathetic neuronal synaptogenesis and impulse activity ordinarily undergo their most rapid development. Most of the 6-hydroxydopamine-induced differences in nucleic acids lessened or disappeared toward weaning, and thus these data support the view that sympathetic neuronal input influences the timing of maturational control of macromolecules, but not their final set-point. In combination with earlier studies showing termination of DNA synthesis caused by exposure of heart and kidney acutely to high levels of catecholamines, the results suggest that neuronal activity provides a biphasic signal, with positive trophic effects predominating during early development when sympathetic tone is low, and negative effects appearing when sympathetic tone is elevated during the late preweanling stage.
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D004247:DNA / Q000032:analysis; D004298:Dopamine / Q000378:metabolism; D006321:Heart / Q000254:growth & development / Q000294:innervation*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007668:Kidney / Q000254:growth & development / Q000294:innervation*; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D006892:Hydroxydopamines; D011506:Proteins; D012313:RNA; D016627:Oxidopamine; D004247:DNA; D004298:Dopamine; D009638:Norepinephrine