Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring.
Low birth weight humans often exhibit hypertension during adulthood. Studying the offspring of rat dams fed a maternal low-protein diet is one model frequently used to study the mechanisms of low birth weight-related hypertension. It remains unclear whether this model replicates key clinical findings of hypertension and increased blood pressure responsiveness to stress or high-salt diet. We measured blood pressure via radiotelemetry in 13-wk-old male offspring of maternal normal- and low-protein dams. Neither group exhibited hypertension at baseline; however, 1 h of restraint was accompanied by a significantly greater blood pressure response in low-protein compared with normal-protein offspring. To enhance the effect of a high-salt diet on blood pressure, normal- and low-protein offspring underwent right uninephrectomy, while controls underwent sham surgery. After 5 weeks on a high-salt diet (4% NaCl), mean arterial pressure in the Low-Protein+Sham offspring was elevated by 6 +/- 2 mmHg (P < 0.05 vs. baseline), while it remained unchanged in the normal-protein offspring. In the two uninephrectomized groups, blood pressure increased further, but was of similar magnitude. Glomerular filtration rate in the low-protein uninephrectomized offspring was 50% less than that in normal-protein offspring with intact kidneys. These data indicate that, while male low-protein offspring are not hypertensive during young adulthood, their blood pressure is hyperresponsive to restraint stress and is salt sensitive, and their glomerular filtration rate is more sensitive to hypertension-causing insults. Collectively, these may predispose for the development of hypertension later in life.
Augustyniak
Robert A
RA
Department of Medicine, Wayne State University, Detroit, MI, USA. augustyn@oakland.edu
Singh
Karan
K
Zeldes
Daniel
D
Singh
Melissa
M
Rossi
Noreen F
NF
D000818:Animals; D001724:Birth Weight / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D018753:Diet, Protein-Restricted; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006977:Hypertension, Renal / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology; D008098:Litter Size / Q000502:physiology; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000503:physiopathology*; D009399:Nephrons / Q000503:physiopathology; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D013312:Stress, Physiological / Q000502:physiology*
D017673:Sodium Chloride, Dietary