Increased leukotriene A(4) hydrolase expression in the heart of angiotensin II-induced hypertensive rat.
Leukotriene A(4) (LTA(4)) hydrolase is essential for the conversion of LTA(4) to LTB(4), an inflammatory lipid mediator. We investigated whether LTA(4) hydrolase was regulated in the heart by angiotensin II (ang II) infusion. Continuous ang II infusion via an osmotic minipump for up to 7 days upregulated mRNA and protein levels of LTA(4) hydrolase ( approximately 3.5-fold of control) in the heart in a pressor-dependent manner. Immunohistochemistry demonstrated intense LTA(4) hydrolase staining in the myofibroblast as well as migrated monocytes/macrophages. These data suggest that the cardiac LTA(4) hydrolase-LTB(4) system plays a positive role in the promotion of cardiac inflammation in hypertension.
Ishizaka
N
N
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo, Japan. nobuishizka-tky@umin.ac.jp
Nakao
A
A
Ohishi
N
N
Suzuki
M
M
Aizawa
T
T
Taguchi
J
J
Nagai
R
R
Shimizu
T
T
Ohno
M
M
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D004851:Epoxide Hydrolases / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D011355:Prodrugs / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D007093:Imidazoles; D011355:Prodrugs; D011725:Pyridines; C112300:TA 606; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase