title: Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.
abstract: Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats.
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee. ageurts@mcw.edu.
authors.forename: Aron M
authors.initials: AM
authors.lastname: Geurts
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: David L
authors.initials: DL
authors.lastname: Mattson
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Erwin
authors.initials: E
authors.lastname: Cabacungan
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Skelton
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Kurth
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Endres
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Jason
authors.initials: J
authors.lastname: Klotz
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.affiliation: From the Departments of Physiology (A.M.G., D.L.M., P.L., M.M.S., T.M.K., C.Y., B.T.E., J.K., M.L., A.W.C.), Pediatrics (E.C.), and Cardiovascular Research Center (A.M.G.), Medical College of Wisconsin, Milwaukee.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000821:Animal Feed / Q000009:adverse effects*; D000818:Animals; D002364:Caseins; D004198:Disease Susceptibility; D002523:Edible Grain; D004624:Embryo Transfer; D005260:Female; D020869:Gene Expression Profiling; D059647:Gene-Environment Interaction; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D007774:Lactation; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000633:toxicity*; D013382:Subtraction Technique
chemical_list: D002364:Caseins; D017673:Sodium Chloride, Dietary
keywords: Dahl salt-sensitive rats; acute renal injury; blood pressure; caseins; hypertension; rats