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The Role of Angiotensin II on Human and Partial Bladder Outlet Obstructed Rabbit Corpus Cavernosal Contractility: Modulation of Nitric Oxide-Mediated Relaxation and Relevance to Erectile Dysfunction

Ertemi, HS; (2013) The Role of Angiotensin II on Human and Partial Bladder Outlet Obstructed Rabbit Corpus Cavernosal Contractility: Modulation of Nitric Oxide-Mediated Relaxation and Relevance to Erectile Dysfunction. Doctoral thesis , UCL (University College London). Green open access

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Abstract

The interaction between angiotensin II (Ang II), a smooth muscle constrictor peptide and nitric oxide (NO) a vasodilator, as well as the role of oxidative stress (OS), have been investigated in human and chronic partial bladder outlet obstructed (PBOO) rabbit corpus cavernosal tissue. The PBOO rabbit model is characterised by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of corpus cavernosal smooth muscle (CCSM) cells, making it a useful model for erectile dysfunction (ED). Immunohistochemical analysis identified Ang II peptide distribution in human corpus cavernosal tissue, while organ bath studies determined the Ang II/NO interaction. OS was determined using apocynin and diphenylene iodonium chloride (DPI), inhibitors of NAD(P)H oxidase, which inhibit superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide). Human penile Ang II was distributed in the arteriolar endothelium, the endothelium lining sinusoids and CCSM cells. The peptide caused a dose dependent contraction of CCSM strips that was inhibited by losartan (AT1 receptor antagonist) and apocynin. In contrast, CCSM relaxation induced by either sodium nitroprusside (SNP, an NO donor) or electrical field stimulation (EFS) was potentiated by losartan. The Ang II contractile response was enhanced in CCSM strips taken from PBOO rabbits and inhibited by losartan, DPI and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil (PDE5 inhibitor) and losartan. Taken together, these findings suggest that Ang II and NO interact to modulate human and rabbit penile smooth muscle tone. Moreover, the Ang II response involves the production of superoxide and the development of OS. The increase in Ang II-mediated CCSM contraction following PBOO is likely to be a pathological consequence of the condition. Importantly, AT1 receptor inhibition may be a therapeutic target for the treatment of ED associated with PBOO.

Type: Thesis (Doctoral)
Title: The Role of Angiotensin II on Human and Partial Bladder Outlet Obstructed Rabbit Corpus Cavernosal Contractility: Modulation of Nitric Oxide-Mediated Relaxation and Relevance to Erectile Dysfunction
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from the ethesis.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/1409849
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