Early-life sodium restriction programs autonomic dysfunction and salt sensitivity in male C57BL/6J mice.

Autor:	Ziegler AA; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Lawton SBR; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Fekete EM; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Brozoski DT; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Wagner VA; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Grobe CC; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Sigmund CD; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Nakagawa P; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Grobe JL; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Comprehensive Rodent Metabolic Phenotyping Core, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Segar JL; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2025 Jan 01; Vol. 328 (1), pp. R109-R120. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1152/ajpregu.00250.2024
Abstrakt:	Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period [postnatal day (PD)21-PD42] programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity. We therefore hypothesized that early-life Na restriction programs changes in cardiovascular control via altered autonomic activity. C57BL/6J male mice were supplied a low (0.04%) Na or supplemented (0.30%) Na diet from PD21 to PD42, before return to standard (0.15%) Na diet. Hemodynamic and autonomic functions were assessed by radiotelemetry and acute administration of autonomic antagonists before and after all animals were switched to a high Na diet (HSD; 1% Na) at 12 wk of age. Mice were additionally treated with the angiotensin II type 1 receptor antagonist losartan for 2 wk. On standard diet, early-life Na restriction resulted in small but significantly different hemodynamic responses to autonomic blockers without any effect on systolic blood pressure (SBP) or heart rate. HSD increased SBP in 0.04% but not 0.30% Na mice, accompanied by increased cardiac sympathetic activity. Losartan had a greater BP-lowering effect in early-life Na-restricted mice. Our findings suggest that Na restriction during a critical hypothalamic developmental period programs long-term changes in the autonomic control of cardiovascular functions and may offer insight into the increased risk of cardiovascular disease in former preterm infants. NEW & NOTEWORTHY Mechanisms by which preterm birth increases the risk of adult-onset cardiometabolic diseases are not well understood. The renin-angiotensin system (RAS) has been implicated in the programming of adult disease, although contributors to RAS dysregulation remain to be identified. Findings from this study suggest that failure to maintain postnatal sodium homeostasis during a critical developmental window may contribute to RAS dysregulation and the risk of salt sensitivity of autonomic and cardiovascular function.
Databáze:	MEDLINE
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