Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring

Augustyniak RA, Singh K, Zeldes D, Singh M, Rossi NF. Maternal protein restriction leads to hyperresponsiveness to stress and salt-sensitive hypertension in male offspring. Am J Physiol Regul Integr Comp Physiol 298: R1375-R1382, 2010. First published March 3, 2010; doi: 10.1152/ajpregu.00848.2009.-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.