Pregnancy Blocks the Hypertensinogenic Effect of Ouabain in Sprague‐Dawley Rats

Abstract

Ouabain‐like inhibitors are elevated in ∼50% of patients with essential hypertension and patients with pre‐eclampsia (PE). Prolonged administration of ouabain induces hypertension in Sprague‐Dawley rats. Accordingly, we hypothesized that ouabain might induce PE in otherwise normal pregnant rats. We implanted ouabain pellets subcutaneously in pregnant (E10) and non‐pregnant rats and measured their blood pressures (BP) weekly by tail cuff. After delivery, trunk blood was collected to determine ouabain‐like activity by radioreceptor assay. Ouabain pellets raised BP significantly in non‐pregnant rats (+18.3 mmHg, p<0.05) compared to non‐pregnant controls (+5.4 mmHg). Surprisingly, there was no significant difference in BP between pregnant rats with ouabain and their pregnant controls. Moreover, there was a significant increase in ouabain‐like activity in all pregnant (57.0 ± 3.1 nmoles plasma equiv/L) verses non‐pregnant (12.4 ± 1.1 nmoles plasma equiv/L) rats, irrespective of BP. These data show 1) that normal pregnant rats become resistant to the hypertensive effect of ouabain; 2) the pregnant state is associated with elevated levels of polar ouabain‐like materials that compete with 3H‐ouabain for binding to Na/K‐ATPase. These ouabain‐like factors may act to prevent increases in BP, or oppose the hypotensive effects of pregnancy. Funded by NHLBI 078870/75584, NIGMS Initiative for Minority Student Development Grant (R25‐GM55036), and Procter and Gamble