Effect of estradiol sulfamate (ES-J995) on affinity of hemoglobin for oxygen, cardiovascular function and acid-base balance in ovariectomized rats

Authors: Bauer K.1; Elger W.2; Schneider B.2; Krahl E.2; Bauer R.1

Source: Experimental and Toxicologic Pathology, Volume 55, Number 4, November 2003 , pp. 301-307(7)

Publisher: Urban & Fischer

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Abstract:

Oral administration of estradiol sulfamate (ES, prodrug of estradiol) leads to increased systemic and reduced hepatic effects than estradiol because ES is accumulated in erythrocytes. However, possible alterations of erythrocytic oxygen transport by intraerythrocytic ES accumulation has not been studied. Therefore, ovariectomized adult female rats (n = 58; body wt.) were randomly treated orally either with single doses (day 1) or multiple dose (days 1–4) with vehicle, with estradiol sulfamate (ES-J995, 1 mg · kg–1 b.w.) or with estradiol (30 mg · kg–1 b.w.). Under general anesthesia arterial blood pressure, heart rate, blood gases, and acid-base balance were measured. Hypoxia was performed by lowering the inspired fraction of oxygen from 0.35 to 0.12. In addition, individual oxygen dissociation curves and ES-J995 distribution in blood and plasma were estimated. ES-J995 was accumulated in erythrocytes by sim98% (P < 0.01), but oxygen transport capacity was not altered (P50: 35.6 ± 1.0 mm Hg to 37.1 ± 1.1 mm Hg). Blood gases and acid-base balance parameters were not altered after ES-J995 treatment under normoxic and hypoxic conditions. In conclusion, ES-J995 accumulation in erythrocytes does not alter the affinity of hemoglobin for oxygen nor any function which would indicate an impaired oxygen delivery to the body.

Document Type: Research article

DOI: 10.1078/0940-2993-00330

Affiliations: 1: Institute for Pathophysiology, Friedrich Schiller University Jena, Germany 2: EnTec GmbH Hamburg/Jena, Jena, Germany

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