Aldosterone-binding globulin-induced hypertension in the rat. A new experimental model.
A thermostable urinary homologue of the plasma aldosterone-binding globulin (ABG), designated ABG-TsU, was isolated and purified by differential ultrafiltration, ion exchange chromatography, and gel filtration to electrophoretic homogeneity. Scatchard plot analysis using highly purified ABG-TsU demonstrated reversible high-affinity low-capacity binding at separate sites for aldosterone and dehydroepiandrosterone sulfate (DHEA-SO4). ABG-TsU injected intraperitoneally (i.p.) in male rats resulted in sustained hypertension after 5 to 8 days, characterized after 12 days by no changes in plasma Na+ K+, aldosterone, or plasma renin activity (PRA). No histological changes could be detected in the kidneys, brains, or hearts, nor evidence of adrenocortical hyperplasia. This hypertension appears to be aldosterone-dependent since it is prevented by bilateral adrenalectomy or administration of a spironolactone, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU. Hemodynamic characterization of this hypertension was carried out in rats after treatment with ABG-TsU or saline i.p. for 14 days. Cardiac output (CO) was measured using the reference sample microsphere method. ABG-TsU-treated rats had significantly higher mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and CO, while no difference in total peripheral resistance (TPR) was detected. This new animal model of borderline essential hypertension (EH) induced by ABG-TsU, which has a reversible high-affinity binding for aldosterone, results in adrenal-dependent hypertension due at this early phase to an increase in CO without any change in TPR, which remains inappropriately normal.
D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001665:Binding Sites; D002302:Cardiac Output; D002352:Carrier Proteins; D004195:Disease Models, Animal; D006439:Hemodynamics; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012712:Serum Globulins; D012964:Sodium / Q000097:blood
D002352:Carrier Proteins; D012712:Serum Globulins; C488874:aldosterone-binding globulin protein, rat; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D011188:Potassium