Angiotensin II type AT2 receptor mRNA expression and renal vasodilatation are increased in renal failure

被引:38
作者
Bautista, R
Sánchez, A
Hernández, J
Oyekan, A
Escalante, B [1 ]
机构
[1] IPN, Ctr Invest & Estudios Avanzados, Dept Mol Biomed, Mexico City 07360, DF, Mexico
[2] Texas So Univ, Coll Pharm & Hlth Sci, Ctr Cardiovasc Dis, Houston, TX 77004 USA
关键词
receptors; angiotensin; cytochrome P450; kidney failure; angiotensin II; arachidonic acid;
D O I
10.1161/hy09t1.096186
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Kidney failure is associated with changes in renal vascular responses to angiotensin (Ang) II. We characterized expression of Ang II receptors and the renal vasoconstrictor and vasodilator responses to Ang II in kidneys from sham-operated and kidney failure rats. In the isolated perfused kidney of sham-operated rats, Ang II (1, 2, 4, and 8 ng) increased perfusion pressure by 27 +/-6, 41 +/- 10, 54 +/- 11, and 74 +/- 12 mmHg, respectively. These responses were amplified by 62 +/- 10% (P <0.05) in kidney failure rats. Losartan (1 mu mol/L), an angiotensin type 1 (AT(1)) receptor blocker, abolished renal vasoconstriction induced by Ang 11, unmasking a renal vasodilatation that was greater in kidney failure rats. CGP-42112 (1 mu mol/L) or PD 123,319 (1 mu mol/L), angiotensin type 2 (AT(2)) receptor ligands, blunted Ang II-induced renal vasodilatation. In the renal tissue of kidney failure rats, there was a marked increase in expression of AT(1) and AT(2) mRNA receptor. Ang II-induced vasodilatation was blunted by eicosatetraynoic acid (1 mu mol/L), the all-purpose inhibitor of arachidonic acid metabolism; clotrimazole (1 mu mol/L), an inhibitor of epoxygenase-dependent arachidonic acid metabolism; or N omega -nitro-L-arginine methyl ester (L-NAME; 1 mu mol/L), an inhibitor of NO synthesis. On stimulation with Ang II, 20-HETE was the predominant product released into the renal effluent of sham-operated rats, whereas epoxy-eicosatrienoic acids were the predominant products released into the effluent of kidney failure rats. These data suggest that during development of kidney failure, there is induction of the AT(2) receptors, which may account for increased Ang II-dependent vasodilatation through the predominant release of epoxyeicosatrienoic acids.
引用
收藏
页码:669 / 673
页数:5
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