High intraluminal pressure via increased release of hydrogen peroxide maintains arteriolar responsiveness to angiotensin II

Abstract

Previously we have found that high intraluminal pressure itself, upregulates several components of the renin-angiotensin system in the arterial wall. We hypothesized, that exposure of vessels to high intraluminal pressure alters angiotensin II (Ang II)-induced constrictions. We have found that in isolated rat skeletal muscle arterioles (~ 150 μm) Ang II-induced constrictions decreased by the second application (from 59±4% to 26±5%, at 10−8 M, p<0.05), if the intraluminal pressure was maintained at normotensive level (80 mmHg). In contrast, if arterioles were exposed to high intraluminal pressure (160 mmHg, for 30 min) Ang II-induced constrictions remained substantial upon second application (51±3% at 10−8 M). Responses to norepinephrine (10−7 M) and acetylcholine (10−7 M) were unaffected by the levels of intraluminal pressure. In the presence PEG-catalase, known to reduce the level of hydrogen peroxide (H2O2), second application of Ang II evoked similarly reduced constrictions after high pressure exposure (29±4% at 10−8 M). Next, arterioles were exposed to exogenous H2O2 (80 mmHg, for 30 min, 10−6 M). In this condition Ang II-induced constrictions remained substantial upon second application (59±5% at 10−8 M). These findings indicate that high intraluminal pressure via an increased H2O2 production maintains the responsiveness of isolated skeletal muscle arterioles to Ang II. Supported by AHA NE Aff. 0555897T and Hungarian NSRF/OTKA -T48376 and HSC/ETT 364/2006.