Excessive maternal salt intake gives rise to vasopressin-dependent salt sensitivity of blood pressure in male offspring. (January 2021)

• Record Type: Journal Article
• Authors: Kim, Young-Beom; Jung, Won Woo; Lee, Seung Won; Jin, Xiangyan; Kang, Hyung Kyung; Hong, Eun-Hwa; Min, Sun Seek; Kim, Yoon-Sik; Han, Hee Chul; Colwell, Christopher S.; Kim, Yang In
• Is Part Of: Journal of molecular and cellular cardiology. Volume 150(2021)
• Page Start: 12
• Page End: 22
• Publication Date: 2021-01
• Subjects: Salt-sensitivity of blood pressure -- Vasopressin -- GABA -- Hypertension -- Magnocellular AVP neurons; SSBP Salt sensitivity of blood pressure -- AVP arginine-vasopressin -- BP blood pressure -- BV blood volume -- CO cardiac output -- RAAS renin-angiotensin-aldosterone system -- SNS sympathetic nervous system -- [Na+] sodium concentration -- CSF cerebrospinal fluid -- ACSF artificial CSF -- SON supraoptic nucleus -- [Cl−]i intracellular Cl−concentration -- AP5, NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid -- DNQX, non-NMDA receptor antagonist 6, 7-dinitroquinoxaline-2, 3-dione -- ANCOVA analysis of covariance -- ANOVA analysis of variance -- SBP systolic blood pressure -- EGABA GABA equilibrium potential -- DFGABA, defined as EGABA – resting membrane potential GABA driving force; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2020.09.013
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: 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. Graphical abstract: Unlabelled Image Highlights: Maternal salt intake during pregnancy programs salt-sensitivity in male offspring. Vasopressin secretion plays a crucial role in driving salt-sensitivity. GABA excitation in vasopressin neurons contributes to vasopressin secretion.