Salt sensitivity of blood pressure (SSBP) is a trait carrying strong prognostic implications for various cardiovascular diseases. To test the hypothesis that excessive maternal salt intake causes SSBP in offspring through a mechanism dependent upon arginine-vasopressin (AVP), we performed a series of experiments using offspring of the rat dams salt-loaded during pregnancy and lactation with 1.5% saline drink (“experimental offspring”) and those with normal perinatal salt exposure (“control offspring”). Salt challenge, given at 7–8 weeks of age with either 2% saline drink (3 days) or 8% NaCl-containing chow (4 weeks), had little or no effect on systolic blood pressure (SBP) in female offspring, whereas the salt challenge significantly raised SBP in male offspring, with the magnitude of increase being greater in experimental, than control, rats. Furthermore, the salt challenge not only raised plasma AVP level more and caused greater depressor responses to V1a and V2 AVP receptor antagonists to occur in experimental, than control, males, but it also made GABA excitatory in a significant proportion of magnocellular AVP neurons of experimental males by depolarizing GABA equilibrium potential. The effect of the maternal salt loading on the salt challenge-elicited SBP response in male offspring was precluded by maternal conivaptan treatment (non-selective AVP receptor antagonist) during the salt-loading period, whereas it was mimicked by neonatal AVP treatment. These results suggest that the excessive maternal salt intake brings about SSBP in male offspring, both the programming and the expression of which depend on increased AVP secretion that may partly result from excitatory GABAergic action.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) to Y. I Kim ( 2014R1A2A1A11049900 , 2017R1A2B2002277 ) and Y.-B. Kim ( 2019R1I1A1A01057744 ) and by the Korea University grant to Y.-B. Kim. W.W.J, S.W.L., X.J. and Y.I.K. were supported by the Brain Korea 21 Project from 2009 to 2019.
© 2020 Elsevier Ltd
- Magnocellular AVP neurons
- Salt-sensitivity of blood pressure
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine