L-arginine reverses renin, hypertension, and electrolyte excretion changes in pregnancy induced hypertensive rats

Abstract

Pregnancy-induced hypertensive (PIH) disorders are a leading cause of maternal mortality and fetal morbidity. Spontaneous sustained hypertension and intrauterine growth restriction often characterize these disorders. The SHHF/Mcc-facp (SHHF) has been used as an animal model of the human disorders because it has the above features plus abnormal gene expression in the placental and kidney. Although the mechanisms responsible for PIH are unknown, altered function of the renin-angiotensin system (RAS) has been implicated. To gain a molecular understanding of the role of the RAS in spontaneous PIH in SHHF rats, kidney mRNA expression profile of RAS components at gestation day 20 were compared with normotensive pregnant WKY controls. By gestation day 10, systolic blood pressure was 40 ± 5 mm Hg higher than pre-pregnant values compared to hypotension in pregnant WKY and remained elevated for the duration of pregnancy. Na and Ca excretion were lower than WKY controls despite higher blood pressure. PRA was significantly lower in SHHF rats (2.1 ± 0.1 ng/ml.hr vs 9.7 ± 1.3 ng/ml.hr, p<0.05) and renin mRNA was downregulated 66± 7% compared to pregnant WKY. Although AGT mRNA was undetectable in SHHF rat kidney, ACE RnBP, and AT1 receptor were all highly expressed. L-arginine administration beginning on day 1 reversed changes in blood pressure, Na and Ca excretion, as well as renin mRNA expression, suggesting that there may be an association between Na, Ca, and renin in PIH. L-arginine did not alter abundance of AGT, RnBP, ACE, or AT1receptor mRNA, suggesting that regulation of renin expression and Na and Ca expression in PIH rats may be mediated by the NO pathway. We conclude that the impaired RAS in PIH rats is at the level of renin gene expression and that this impairment may be reversed by L-arginine.