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Angiotensin II‐induced modulation of endothelium‐dependent relaxation in rabbit mesenteric resistance arteries
Author(s) -
Itoh Takeo,
Kajikuri Junko,
Tada Toyohiro,
Suzuki Yoshikatsu,
Mabuchi Yoshio
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j..2003.t01-1-00893.x
Subject(s) - rabbit (cipher) , mesenteric arteries , angiotensin ii , endothelium , medicine , endocrinology , chemistry , cardiology , biophysics , biology , artery , receptor , mathematics , statistics
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 (AT 1 R) and angiotensin converting enzyme (ACE) was confirmed in these arteries. In endothelium‐intact strips, the AT 1 R‐blocker olmesartan (1 μ m ) and the ACE‐inhibitor temocaprilat (1 μ m ) each enhanced the ACh (0.03 μ m )‐induced relaxation during the contraction induced by noradrenaline (NA, 10 μ m ). Similar effects were obtained using CV‐11974 (another AT 1 R 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 n m ). 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 β‐escin‐skinned strips, 8‐bromoguanosine 3′,5′ cyclic monophosphate (8‐Br‐cGMP, 0.01–1 μ m ) concentration dependently inhibited the contractions induced (a) by 0.3 μ m Ca 2+ in the presence of NA+GTP and (b) by 0.2 μ m Ca 2+ +GTPγS. Olmesartan significantly enhanced, while Ang II (0.1 n m ) 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 AT 1 Rs and inhibits ACh‐induced, endothelium‐dependent relaxation at least partly by inhibiting the action of cGMP on these cells.