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

Shuji Arima, Yoshimi Endo, Hiraku Yaoita, Ken Omata, Susumu Ogawa, Kazuo Tsunoda, Michiaki Abe, Kazuhisa Takeuchi, Keishi Abe, Sadayoshi Ito

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154 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2816-2823
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number11
DOIs
Publication statusPublished - 1997 Dec 1

Keywords

  • Arachidonic acid
  • Cytochrome P-450 epoxygenase
  • Endothelium
  • Glomerular hemodynamics
  • Miconazole

ASJC Scopus subject areas

  • Medicine(all)

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