Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole
Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole
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DOI：
10.1172/jci119829
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发表时间：
1997-12-01
影响因子：
15.9
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Arima, S;Endo, Y;Ito, S
尽管血管紧张素 II 2 型 (AT(2)) 受体最近已被克隆，但其功能作用尚不清楚。我们测试了这样的假设：选择性激活 AT(2) 受体会导致肾小球前传入小动脉 (Af-Art) 的血管舒张，该血管段是肾小球前阻力的主要来源。我们在体外以 60 mmHg 对兔 Af-Arts 进行微灌注，并在存在或不存在 Ang II 1 型受体拮抗剂 CV11974 (CV; 10(-8) M) 的情况下检查血管紧张素 II (Ang II; 10(-11)-10(-8) M) 对管腔直径的影响。将 Ang II 添加到预收缩 Af-Arts 的浴和管腔中，Ang II 进一步收缩无 CV 的 Af-Arts（在 10(-8) M 时比预收缩水平高 74 +/- 7%；P < 0.01，n = 7）。相反，在存在 CV 的情况下，Ang II 会引起剂量依赖性扩张； 10(-8) M 的 Ang II 使直径增加 29 +/- 2% (n = 7, P < 0.01)。这种扩张通过 AT(2) 受体拮抗剂 PD123319 (10(-7) M, n = 6) 预处理完全消除，表明 AT(2) 受体的激活导致 Af-Arts 中的血管舒张。抑制一氧化氮合酶 (n = 7) 或环氧合酶 (n = 7) 不会影响扩张，但是，通过破坏内皮 (n = 7) 可以消除这种扩张。 10) 或抑制细胞色素 P-450 途径，特别是环氧二十碳三烯酸 (EET，n = 7) 的合成，这些结果表明，在 Af-Art 中，AT(2) 受体的激活可能通过细胞色素 P-450 途径（可能是 EET）引起内皮依赖性血管舒张。
Although angiotensin II type 2 (AT(2)) receptor has recently been cloned, its functional role is not well understood. We tested the hypothesis that selective activation of AT(2) receptor causes vasodilation in the preglomerular afferent arteriole (Af-Art), a vascular segment that accounts for most of the preglomerular resistance. We microperfused rabbit Af-Arts at 60 mmHg in vitro, and examined the effect of angiotensin II (Ang II; 10(-11)-10(-8) M) on the luminal diameter in the presence or absence of the Ang II type 1 receptor antagonist CV11974 (CV; 10(-8) M). Ang II was added to both the bath and lumen of preconstricted Af-Arts, Ang II further constricted Af-Arts without CV (by 74 +/- 7% over the preconstricted level at 10(-8) M; P < 0.01, n = 7). In contrast, in the presence of CV, Ang II caused dose-dependent dilation; Ang II at 10(-8) M increased the diameter by 29 +/- 2% (n = 7, P < 0.01). This dilation was completely abolished by pretreatment with an AT(2) receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT(2) receptor causes vasodilation in Af-Arts, The dilation was unaffected by inhibiting either nitric oxide synthase (n = 7) or cyclooxygenase (n = 7), however, it was abolished by either disrupting the endothelium (n = 10) or inhibiting the cytochrome P-450 pathway, particularly the synthesis of epoxyeicosatrienoic acids (EETs, n = 7), These results suggest that in the Af-Art activation of the AT(2) receptor may cause endothelium-dependent vasodilation via a cytochrome P-450 pathway, possibly by EETs.