Chronic intermittent hypobaric hypoxia antagonizes renal vascular hypertension by enhancement of vasorelaxation via activating BKCa.

ABSTRACT

AIM: The purpose of the present study was to explore anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in renovascular hypertension (RVH) rats, as well as the role of large-conductance calcium-activated potassium channel (BKCa) in anti-hypertensive effect of CIHH. MAIN METHODS: Male adult age- and body weight-matched Sprague-Dawley rats were divided into SHAM, CIHH, RVH and RVH+CIHH groups. Hypertension was induced by two-kidney-1-clip method (2K1C) in RVH rats. CIHH rats were exposed to 28-days hypobaric hypoxia simulating 5000m altitude, 6h daily. SHAM rats got an operation without 2K1C, and RVH+CIHH rats received CIHH treatment after 2K1C. The endothelium-dependent vasorelaxation induced by acetylcholine (ACh), BKCa currents in smooth muscle cells (VSMCs) of mesenteric arteries and the protein expression of BKCa in mesenteric arteries was examined. KEY FINDINGS: The systolic arterial blood pressure (SAP) in RVH rats was higher than that in SHAM rats and CIHH treatment significantly decreased SAP in RVH rats. The enhanced vasorelaxation of mesenteric artery in CIHH-treated RVH rats was cancelled by BKCa blocker IBTX. The vasorelaxation induced by BKCa activator was reduced in RVH rats and the decreased vasorelaxation was improved by CIHH treatment. The ß1 subunit of BKCa in mesenteric artery was upregulated and BKCa current in VSMCs was increased in CIHH-treated RVH rats compared with RVH rats. SIGNIFICANCE: In conclusion, CIHH treatment enhances the relaxation of mesenteric artery through activation of BKCavia up-regulating ß1 subunit of BKCa, which might be one of mechanisms for anti-hypertensive effect of CIHH in RVH rats.