Salt-sensitive hypertension: food for thought.

E pidemiological studies demonstrating an increase in cardiovascular disease in adult children born of women who suffered nutritional privation during World War II led to many subsequent studies, demonstrating that diverse conditions leading to intrauterine growth retardation had similar effects on cardiovascular disease including hypertension. 1 Relatively mild maternal protein deficiency leads to abnormal nephron structure and dysregulation of the renin–angiotensin II–aldosterone system. The report in this issue, by Geurts et al 4 builds on the finding that a protein-sufficient casein-based diet significantly increases the degree of salt-induced hyper-tension and renal damage in the inbred Dahl Salt-Sensitive rat strains SS/Mcw when compared with SS/Crl fed a grain-based diet with similar proportions of protein, fat, and carbohydrates. 5 SS/Mcw rats were derived from Dahl SS/Jr rats purchased from Harlan Sprague Dawley Laboratories and maintained by brother-sister mating at the Medical College of Wisconsin since 1991, where they were fed a purified diet using casein as the protein source. SS/Crl rats were derived from SS/Mcw given to Charles River Laboratories in 2001 and fed a grain-based diet. In the present study, progeny of 4-way embryo transfers between SS/Mcw and SS/Crl dams fed their usual diets, progeny of parental strains on their usual diets, and SS/Crl rats after 1 generation of the purified casein-based diet were studied with or without 3 weeks on a high casein-based diet. Blood pressure, albuminuria, renal histopa-thology, and transcriptome analyses of the outer renal cortex were compared. The degree of pathology induced by high-salt consumption in the progeny of embryo transfers correlated with the diet of the recipient dam, thus the gestational and lactational environment, rather than genetic background. Rats of both strains experiencing the gestational and lactational environment of SS/Mcw dams fed the casein-based diet had similar hypertension and renal pathology on salt challenge as the SS/Mcw controls, which was significantly greater than that of rats of either strain transferred to SS/McwClr dams fed the grain-based chow. Similarly, the response of SS/Crl fed the casein-based diet for one generation to high salt was the same as that of SS/Mcw rats fed the diet for many generations. The complex comparisons of transcriptomes is an admirable tour de force. The most significant differences in the transcriptomes of the outer renal medulla between the different groups, with and without salt challenge, were attributable to the protein source in the different diets and were similar to those obtained in the previous …