Sustained increases in plasma C-type natriuretic peptides fail to increase concentrations in cerebrospinal fluid: Evidence from pregnant sheep.
C-type natriuretic peptide (CNP) is a paracrine growth factor with high abundance in CNS tissues and cerebrospinal fluid (CSF). Consistent with findings of CNP transcripts in the cerebral microvasculature and hypothalamus, CNP increases the permeability of the blood-brain barrier and reduces food intake when administered intracerebroventricularly in rodents. Whether high concentrations of CNP in plasma can affect CSF levels is unknown. Accordingly we have studied changes (days 4, 87 and 116) in concurrent plasma and CSF concentrations of CNP peptides in pregnant sheep - a physiologically unique setting in which plasma CNP is elevated for prolonged periods. Preliminary studies in non pregnant sheep showed stable CNP levels in CSF during repetitive sampling. Compared with values in non pregnant controls, plasma concentrations of CNP peptides were markedly raised (30-fold) at days 87 and 116 in pregnant sheep, yet CSF levels in the two groups did not differ. CNP peptides in CSF decreased from day 4 to day 87 in pregnant sheep, possibly reflecting an adaptive response of the cerebral vasculature to increased hemodynamic load. We conclude that sustained high concentrations of CNP - far exceeding levels encountered in human pathophysiology - fail to affect CNP peptide levels in CSF.
Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647 Christchurch, New Zealand. Electronic address: michele.wilson@lincolnuni.ac.nz.
Michele O
MO
Wilson
Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln 7647 Christchurch, New Zealand.
Graham K
GK
Barrell
Department of Medicine, University of Otago, Christchurch 8140, New Zealand.
Timothy C R
TC
Prickett
Department of Medicine, University of Otago, Christchurch 8140, New Zealand.
Eric A
EA
Espiner
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D020098:Natriuretic Peptide, C-Type / Q000097:blood / Q000134:cerebrospinal fluid; D011247:Pregnancy; D012756:Sheep
D020098:Natriuretic Peptide, C-Type
Blood–brain barrier; C-type natriuretic peptide; Cerebrospinal fluid, NTproCNP, Pregnancy