Angiotensin II-stimulated nitric oxide release from porcine pulmonary endothelium is mediated by angiotensin IV

Nathalie Hill-Kapturczak, Matthias H. Kapturczak, Edward R. Block, Jawaharlal M. Patel, Tadeusz Malinski, Kirsten M. Madsen, C. Craig Tisher

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

In this study, a nitric oxide (NO) sensor was used to examine the ability of angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to explore the mechanism of the AngII-stimulated NO release. Physiologic concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In contrast, Bk, but not AngII, stimulated NO release from PAE cells, AngII-stimulated NO release from PPAE cells required extracellular L- arginine and was inhibited by L-nitro-arginine methyl ester. AT1 and AT2 receptor inhibition had no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV, an AngII metabolite with binding sites that are pharmacologically distinct from the classic AngII receptors, stimulated considerably greater NO release and greater endothelial-type constitutive NOS activity than the same amount of AngII. The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV-mediated NO release as well as NOS activation. The results demonstrate that AngIV and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO release and the associated endothelium-dependent vasorelaxation. Furthermore, these results suggest that differences exist in both AngII- and Bk-mediated NO release between PPAE and PAE cells, which may reflect important differences in response to these hormones between vascular beds.

Original languageEnglish (US)
Pages (from-to)481-491
Number of pages11
JournalJournal of the American Society of Nephrology
Volume10
Issue number3
StatePublished - Mar 1999
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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