RT Journal Article
SR Electronic
T1 Beneficial Effects of Metolazone in a Rat Model of Preeclampsia
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1027
OP 1032
DO 10.1124/jpet.106.104901
VO 318
IS 3
A1 Gabriella Pridjian
A1 Candice Pridjian
A1 Svitlana Danchuk
A1 Monica Ianosi-Irimie
A1 Hop V. Vu
A1 Jules B. Puschett
YR 2006
UL http://jpet.aspetjournals.org/content/318/3/1027.abstract
AB Preeclampsia is a disorder that continues to exact a significant toll with respect to maternal morbidity and mortality as well as fetal wastage. Furthermore, the treatment of this disorder has not changed significantly in 50 years and is unsatisfactory. The use of diuretics in this syndrome is controversial because there is a concern related to potential baleful effects of volume contraction leading to a possible further decrement in the perfusion of the maternal-fetal unit. Metolazone is a diuretic/antihypertensive agent, which has a therapeutic effect on blood pressure (BP) in human essential hypertension without causing a natriuresis. We administered the drug in nondiuretic doses in a rat model of preeclampsia previously developed in this laboratory. The drug reduced BP without an accompanying natriuresis. Although there was a trend toward an improvement in intrauterine growth restriction, as determined by litter size and the number of pups demonstrating malformations, the values did not reach statistical significance. We conclude that metolazone, in low dosage, is an effective antihypertensive in this rat model. These studies have implications for the treatment of the human disorder. The American Society for Pharmacology and Experimental Therapeutics