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This Article Full Text Full Text (PDF) All Versions of this Article: 548/3/893    most recent 2002.034116v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Itoh, T. Articles by Mabuchi, Y. Search for Related Content PubMed PubMed Citation Articles by Itoh, T. Articles by Mabuchi, Y.

Angiotensin II-induced modulation of endothelium-dependent relaxation in rabbit mesenteric resistance arteries

Takeo Itoh*, Junko Kajikuri*, Toyohiro Tada†, Yoshikatsu Suzuki‡ and Yoshio Mabuchi§

The role of local endogenous angiotensin II (Ang II) in endothelial function in resistance arteries was investigated using rabbit mesenteric resistance arteries. First, the presence of immunoreactive Ang II together with Ang II type-1 receptor (AT₁R) and angiotensin converting enzyme (ACE) was confirmed in these arteries. In endothelium-intact strips, the AT₁R-blocker olmesartan (1 µM) and the ACE-inhibitor temocaprilat (1 µM) each enhanced the ACh (0.03 µM)-induced relaxation during the contraction induced by noradrenaline (NA, 10 µM). Similar effects were obtained using CV-11974 (another AT₁R blocker) and enalaprilat (another ACE inhibitor). The nitric-oxide-synthase inhibitor N^G-nitro-L-arginine (L-NNA) abolished the above effect of olmesartan. In endothelium-denuded strips, olmesartan enhanced the relaxation induced by the NO donor NOC-7 (10 nM). Olmesartan had no effect on cGMP production (1) in endothelium-intact strips (in the absence or presence of ACh) or (2) in endothelium-denuded strips (in the absence or presence of NOC-7). In -escin-skinned strips, 8-bromoguanosine 3',5' cyclic monophosphate (8-Br-cGMP, 0.01-1 µM) concentration dependently inhibited the contractions induced (a) by 0.3 µM Ca²⁺ in the presence of NA+GTP and (b) by 0.2 µM Ca²⁺+GTPS. Olmesartan significantly enhanced, while Ang II (0.1 nM) significantly inhibited, the 8-Br-cGMP-induced relaxation. We propose the novel hypothesis that in these arteries, Ang II localized within smooth muscle cells activates AT₁Rs and inhibits ACh-induced, endothelium-dependent relaxation at least partly by inhibiting the action of cGMP on these cells.