Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole

K. Kohagura, Y. Endo, Osamu Ito, S. Arima, K. Omata, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Nitric oxide (NO) and epoxyeicosatrienoic acids (EETs), cytochrome P450 epoxygenase metabolites of arachidonic acid, are released by the vascular endothelium and play important roles in the control of glomerular haemodynamics. We examined whether endogenous NO or EETs modulate angiotensin II- (AngII) induced constriction in isolated microperfused afferent arteriole (Af-Art) of the rabbit kidney. When Af-Arts were treated with N(G)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthese; 10-4 mol L-1) or miconazole (an inhibitor of P450 epoxygenase; 10-6 mol L-1), basal diameter was decreased by 34.5 ± 2.2 and 13.9 ± 3.2%, respectively. AngII added to both the bath and lumen decreased the diameter of Af-Arts in a dose-dependent manner. Pretreatment with either L-NAME or miconazole also augmented the constrictor response to AngII. AngII at 10-8 mol L-1 decreased the diameter to 39.2 ± 1.4, 32.9 ± 3.6, and 12.7 ± 4.6%, in control, L-NAME-, and miconazole-treated group, respectively. In order to study whether the AngII type2 (AT2) receptor modulates AngII action via NO or EETs, we repeated the experiments in the presence of PD123319 (an AT2 receptor antagonist; 10-7 mol L-1). In the presence of PD123319, L-NAME still augmented the constrictor response to AngII, however, miconazole had no effect. In the presence of PD123319, AngII at 10-8 mol L-1 decreased the diameter to 25.0 ± 4.6, 9.4 ± 4.0, and 26.0 ± 3.3%, in control, L-NAME-, and miconazole-treated group, respectively. These results suggest that (1) tonic release of NO and EETs attenuates the vasoconstrictor response to AngII in Af-Arts and (2) AT2 receptor seems to be coupled to EETs rather than the NO pathway.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalActa Physiologica Scandinavica
Volume168
Issue number1
DOIs
Publication statusPublished - 2000 Mar 14

Keywords

  • Afferent arteriole
  • Angiotensin II
  • Endothelium
  • Epoxyeicosatrienoic acids
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology

Fingerprint

Dive into the research topics of 'Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole'. Together they form a unique fingerprint.

Cite this