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Pregnancy and Pseudopregnancy: Physiological States with High Endogenous Ouabain, Coexistent Suppression of Maternal Arterial Myocyte NCX and α2 Na+ Pumps, and Resistance to Ouabain‐Induced Hypertension
Author(s) -
Jacobs Brandiese E,
Liu Yong,
Zulian Alessandra M,
Golovina Vera A,
Hamlyn John M
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.982.18
Subject(s) - ouabain , medicine , endocrinology , blood pressure , endogeny , pregnancy , chemistry , myocyte , biology , sodium , organic chemistry , genetics
Endogenous ouabain (EO) is elevated and correlates with blood pressure (BP) in ~50% of patients with essential hypertension. “Ouabain‐like” inhibitors are increased in pre‐eclampsia (PE) and correlate with BP. EO and ouabain inhibit the α2‐Na + pump isoform in arterial myocytes, enhance Ca 2+ entry via NCX1.3, and raise BP. We explored whether EO per se is elevated in pregnancy and pseudopregnancy (PSP) and determined whether exogenous ouabain induces PE in otherwise normal pregnant rats. We implanted mini‐osmotic pumps containing ouabain in pregnant (E10), non‐pregnant, and PSP rats and measured BP by tail cuff. At E20 or equivalent, blood, adrenals, and aortas were collected to determine ouabain (RIA), ouabain‐like materials (RRA), NCX, and α2‐Na + pump expression (Western blot). Plasma EO increased in pregnant (4.7 ± 1.9 nM plasma equiv) vs non‐pregnant (0.3 ± 0.02 nM plasma equiv, p<0.001) rats and was confirmed by HPLC‐RIA and mass spectrometry. Adrenal EO content was lower in pregnant (12.3 ± 5.0 nmoles/kg) vs non‐pregnant rats (32.5 ± 15.3 nmoles/kg, p<0.01). NCX and α2‐Na + pump expression decreased in pregnancy. Ouabain infusion raised BP in non‐pregnant rats (+21.3 mmHg, p<0.01), but had no effect on BP in their pregnant or PSP counterparts. These data show: 1) that the pregnant and PSP conditions are physiologically high EO states; 2) both conditions are associated with the development of a physiological resistance to ouabain that prevents BP from increasing. 3) The mechanism of the ouabain resistance is exclusively maternal, and likely related to decreased expression of, and reduced Ca 2+ entry by, vascular NCX. Failure of the maternal circulation to develop resistance to EO may underlie hypertension in PE.