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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H434    most recent 91477.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Allahdadi, K. J. Articles by Kanagy, N. L. PubMed PubMed Citation Articles by Allahdadi, K. J. Articles by Kanagy, N. L.

Endothelin type A receptor antagonist normalizes blood pressure in rats exposed to eucapnic intermittent hypoxia

¹Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico, Health Sciences Center, Albuquerque, New Mexico; ²Department of Pediatrics, The Ohio State University, Columbus, Ohio; and ³Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Submitted 14 December 2007 ; accepted in final form 22 May 2008

We have reported that eucapnic intermittent hypoxia (E-IH) causes systemic hypertension, elevates plasma endothelin 1 (ET-1) levels, and augments vascular reactivity to ET-1 and that a nonspecific ET-1 receptor antagonist acutely lowers blood pressure in E-IH-exposed rats. However, the effect of chronic ET-1 receptor inhibition has not been evaluated, and the ET receptor subtype mediating the vascular effects has not been established. We hypothesized that E-IH causes systemic hypertension through the increased ET-1 activation of vascular ET type A (ET_A) receptors. We found that mean arterial pressure (MAP) increased after 14 days of 7 h/day E-IH exposure (109 ± 2 to 137 ± 4 mmHg; P < 0.005) but did not change in sham-exposed rats. The ET_A receptor antagonist BQ-123 (10 to 1,000 nmol/kg iv) acutely decreased MAP dose dependently in conscious E-IH but not sham rats, and continuous infusion of BQ-123 (100 nmol·kg^–1·day^–1 sc for 14 days) prevented E-IH-induced increases in MAP. ET-1-induced constriction was augmented in small mesenteric arteries from rats exposed 14 days to E-IH compared with those from sham rats. Constriction was blocked by the ET_A receptor antagonist BQ-123 (10 µM) but not by the ET type B (ET_B) receptor antagonist BQ-788 (100 µM). ET_A receptor mRNA content was greater in renal medulla and coronary arteries from E-IH rats. ET_B receptor mRNA was not different in any tissues examined, whereas ET-1 mRNA was increased in the heart and in the renal medulla. Thus augmented ET-1-dependent vasoconstriction via vascular ET_A receptors appears to elevate blood pressure in E-IH-exposed rats.

sleep apnea; BQ-123; BQ-788; mitochondrial ribonucleic acid