We have developed a model of preeclampsia in the rat that has several phenotypic characteristics of human preeclampsia, including hypertension, proteinuria and intrauterine growth restriction. Metolazone (M) is a thiazide-like diuretic/antihypertensive agent that can reduce blood pressure in hypertensive patients without causing a natriuresis. We administered the drug in dosages of 0.05 mg/kg BW to pregnant rats weighing 250-300 g rendered “preeclamptic” by the administration of desoxycorticosterone acetate and replacement of their drinking water with 0.9% saline. The preeclamptic (PDS) group attained mean tail cuff blood pressures (BP) of 128 ± 9 mm Hg at day 17 of pregnancy as compared to a mean value of 92 ± 14 mm Hg in a group given M (PDS + M) in a daily non-natriuretic dose by gastric gavage (p < .01). After normalization for β-actin, Western immunoblot determinations (triplicate) involving 7 PDS and 9 PDS + M animals showed a 36% decrease in the expression of Na/K ATPase in the kidney cortex from PDS + M compared to untreated PDS rats. A 32% decrease in expression in the renal medulla was also seen in the PDS + M animals compared to the PDS group. We conclude that the action of M in the reduction of BP in our “preeclamptic” rat model includes both its effects on Na transporters as well as the expression of the Na/K ATPase enzyme in the kidney.
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