Maternal Low Protein Diet and Fetal Glucocorticoid Exposure Program Adult Murine Cardiovascular and Endocrine Status

Abstract

Fetal programming of human hypertension (HTN) and the metabolic syndrome is associated with low birth weight. We have modeled this process in mice using iso‐caloric low protein (LP) or normal protein (NP) diets provided to dams from E0 to19. Dams on NP received either saline injections or the 11‐βHSD inhibitor carbenoxolone (CX, 12.5mg/g E10 to 19). Offspring were fed either NP or a high fat (HF) diet. Blood pressure (BP) was recorded by radiotelemetry at baseline, on a high salt diet (9% NaCl), or on high salt plus a nitric oxide synthase (NOS) inhibitor (L‐NAME). Dam caloric intake was not altered by LP or CX, but pup birth weight was reduced (LP 1.7 ± 0.1g, CX 1.9 ± 0.1g, NP 2.2 ± 0.2g). Adult female LP and CX offspring had decreased fat pad weight and blood pressure on either NP or high salt (p<0.05). The decrease in BP was blocked by L‐NAME. In contrast, male LP and CX mice had increased fat pad weight and HTN that was exacerbated by both salt and L‐NAME. HF diet increased blood pressure and fat pad weight in NP mice which became similar to LP and CX. Conclusions: LP or CX impair fetal growth and program HTN in male mice. The HTN is partially compensated by NOS activation and is associated with obesity. Female mice are protected from programmed HTN and display decreased adiposity and enhanced NOS activation.