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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/H835    most recent 00205.2008v1 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 Bagi, Z. Articles by Koller, A. PubMed PubMed Citation Articles by Bagi, Z. Articles by Koller, A.

High intraluminal pressure via H₂O₂ upregulates arteriolar constrictions to angiotensin II by increasing the functional availability of AT1 receptors

¹Department of Physiology, New York Medical College, Valhalla, New York; ²Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Debrecen, Hungary; and ³Department of Pathophysiology and Gerontology, University of Pécs, Pécs, Hungary

Submitted 26 February 2008 ; accepted in final form 17 June 2008

Previously, we found that high intraluminal pressure leads to production of reactive oxygen species (ROS) and also upregulates several components of the renin-angiotensin system in the wall of small arteries. We hypothesized that acute exposure of arterioles to high intraluminal pressure in vitro via increasing ROS production enhances the functional availability of type 1 angiotensin II (Ang II) receptors (AT1 receptors), resulting in sustained constrictions. In arterioles (180 µm) isolated from rat skeletal muscle, Ang II elicited dose-dependent constrictions, which decreased significantly by the second application [maximum (max.): from 59% ± 4% to 26% ± 5% at 10^–8 M; P < 0.05] in the presence of 80 mmHg of intraluminal pressure. In contrast, if the arterioles were exposed to high intraluminal pressure (160 mmHg for 30 min), Ang II-induced constrictions remained substantial on the second application (max.: 51% ± 3% at 10^–8 M). In the presence of Tiron and polyethylene glycol (PEG)-catalase, known to reduce the level of superoxide anion and hydrogen peroxide (H₂O₂), second applications of Ang II evoked similarly reduced constrictions, even after high-pressure exposure (29% ± 4% at 10^–8 M). Furthermore, when arterioles were exposed to H₂O₂ (for 30 min, 10^–7 M, at normal 80 mmHg pressure), Ang II-induced constrictions remained substantial on second applications (59% ± 5% at 10^–8 M). These findings suggest that high pressure, likely via inducing H₂O₂ production, increases the functional availability of AT1 receptors and thus enhances Ang II-induced arteriolar constrictions. We propose that in hypertension–regardless of etiology–high intraluminal pressure, via oxidative stress, enhances the functional availability of AT1 receptors augmenting Ang II-induced constrictions.

hypertension; oxidative stress; hydrogen peroxide