8-isoprostane F(2alpha) up-regulates the expression of type 5 phosphodiesterase in cavernosal vascular smooth muscle cells: inhibition with sildenafil, iloprost, nitric oxide and picotamide

MR Hotston, JY Jeremy, R Persad, JWJ Bloor, N Shukla

Research output: Contribution to journalArticle (Academic Journal)

6 Citations (Scopus)

Abstract

OBJECTIVES To explore the possible role of of 8-isoprostane F(2alpha) (8-IPF(2alpha)) in the aetiology of erectile dysfunction (ED), as the over-production of superoxide (O(2) (-)) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase results in the formation of 8-IPF(2alpha) in vascular tissue, which has similar properties to thromboxane A(2) (TXA(2)). TXA(2) is vasoconstrictor and up-regulates the expression of NADPH oxidase and phosphodiesterase type 5 (PDE5). MATERIALS AND METHODS Cavernosal vascular smooth muscle cells (CVSMCs) were incubated with 8-IPF(2alpha) or the TXA(2) analogue, U46619, +/-sildenafil, iloprost (a stable prostacyclin [PGI(2)] analogue) or the nitric oxide (NO) donor NONOate for 16 h. The formation of O(2) (-) was then measured, PDE5 expression assessed using Western blotting and PGI(2) and 8-IPF(2alpha) formation measured using enzyme-linked immunoassays. RESULTS 8-IPF(2alpha) promoted the formation of O(2) (-), an effect inhibited by apocynin (an NADPH oxidase inhibitor) and up-regulated the expression of PDE5. Under identical incubation conditions, 8-IPF(2alpha) induced an increase in the formation of 8-IPF(2alpha) but reduced the formation of PGI(2). All, these effects were reversed by sildenafil, iloprost, NONOate and picotamide. CONCLUSIONS These data show that O(2) (-) derived from NADPH oxidase influences the relative balance of PGI(2) and 8-IPF(2alpha) in CVSMCs, which in turn alters the degree of PDE5 expression. This is a novel pathogenic mechanism underlying ED and a novel mechanism of action of sildenafil.
Translated title of the contribution8-isoprostane F(2alpha) up-regulates the expression of type 5 phosphodiesterase in cavernosal vascular smooth muscle cells: inhibition with sildenafil, iloprost, nitric oxide and picotamide
Original languageEnglish
Pages (from-to)1794 - 1798
Number of pages5
JournalBJU International
DOIs
Publication statusPublished - Dec 2010

Bibliographical note

Publisher: Wiley

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