title: Sustained systemic arterial hypertension induced by extended hypobaric hypoxia.
abstract: Regular administration of recombinant erythropoietin (EPO) is frequently complicated by a rise in arterial blood pressure. We therefore asked if prolonged stimulation of endogenous EPO production has the same effect. To this end, male Sprague-Dawley rats were placed in a hypobaric chamber (390 mm Hg) for 24 days. The control (NL) group was placed in the chamber at normobaric condition. The animals were then removed from the chamber and monitored through day 108. Plasma EPO peaked within 24 hours and returned to baseline by day 7 and remained so thereafter. Hematocrit rose steadily during the hypoxic phase and declined steadily during the normobaric phase, reaching the baseline on day 45. This was accompanied by parallel changes in erythrocyte mass and blood volume. The rise in hematocrit during hypoxia was accompanied by a parallel rise in blood pressure which peaked on day 24. Despite the restoration of normal hematocrit, erythrocyte mass and blood volume following resumption of normoxia, blood pressure remained elevated throughout the observation period. To dissect the role of hypoxia from that of the associated rise in hematocrit, the experiments were repeated using a group of rats whose hematocrits were kept constant by repeated phlebotomies. These animals exhibited a sustained rise in blood pressure identical to that found in the original group. Thus, prolonged hypobaric hypoxia leads to a severe hematocrit-independent systemic hypertension (HTN) that persists long after the restoration of normoxia. Given the transient nature of the rise in its plasma concentration, endogenous EPO does not appear to play a role in the genesis of the observed systemic HTN. The authors believe that this animal model can be used for future studies of the mechanism, consequences and treatment of acquired HTN.
authors.affiliation: Department of Medicine, University of California, Irvine, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Wang
mesh_terms: D000399:Air Pressure; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure; D001810:Blood Volume; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000097:blood; D006400:Hematocrit; D006973:Hypertension / Q000209:etiology*; D000860:Hypoxia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004921:Erythropoietin; D001127:Arginine Vasopressin; D009320:Atrial Natriuretic Factor