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Research Article Free access | 10.1172/JCI119829

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.

S Arima, Y Endo, H Yaoita, K Omata, S Ogawa, K Tsunoda, M Abe, K Takeuchi, K Abe, and S Ito

The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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The Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, 980-77, Japan.

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Published December 1, 1997 - More info

Published in Volume 100, Issue 11 on December 1, 1997
J Clin Invest. 1997;100(11):2816–2823. https://doi.org/10.1172/JCI119829.
© 1997 The American Society for Clinical Investigation
Published December 1, 1997 - Version history
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Abstract

Although angiotensin II type 2 (AT2) receptor has recently been cloned, its functional role is not well understood. We tested the hypothesis that selective activation of AT2 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 AT2 receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT2 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 AT2 receptor may cause endothelium-dependent vasodilation via a cytochrome P-450 pathway, possibly by EETs.

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