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http://purl.uniprot.org/citations/18823320http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18823320http://www.w3.org/2000/01/rdf-schema#comment"

Introduction

The cavernosal tissue is highly responsive to endothelin-1 (ET-1), and penile smooth muscle cells not only respond to but also synthesize ET-1.

Aim

Considering that ET-1 is directly involved in end-organ damage in salt-sensitive forms of hypertension, we hypothesized that activation of the ET-1/ET(A) receptor pathway contributes to erectile dysfunction (ED) associated with mineralocorticoid hypertension.

Methods

Wistar rats were uninephrectomized and submitted to deoxycorticosterone acetate (DOCA)-salt treatment for 5 weeks. Control (Uni [uninephrectomized control]) animals were uninephrectomized and given tap water. Uni and DOCA-salt rats were simultaneously treated with vehicle or atrasentan (ET(A) receptor antagonist, 5 mg/Kg/day). Cavernosal reactivity to ET-1, phenylephrine (PE), ET(B) receptor agonist (IRL-1620) and electric field stimulation (EFS) were evaluated in vitro. Expression of ROCKalpha, ROCKbeta, myosin phosphatase target subunit 1 (MYPT-1), and extracellular signal-regulated kinase 1/2 (ERK 1/2) were evaluated by western blot analysis. ET-1 and ET(A) receptor mRNA expression was evaluated by real-time reverse-transcriptase polymerase chain reaction. Voltage-dependent increase in intracavernosal pressure/mean arterial pressure (ICP/MAP) was used to evaluate erectile function in vivo.

Main outcome measure

ET(A) receptor blockade prevents DOCA-salt-associated ED.

Results

Cavernosal strips from DOCA-salt rats displayed augmented preproET-1 expression, increased contractile responses to ET-1 and decreased relaxation to IRL-1620. Contractile responses induced by EFS and PE were enhanced in cavernosal tissues from DOCA-salt hypertensive rats. These functional changes were associated with increased activation of the RhoA/Rho-kinase and ERK 1/2 pathways. Treatment of rats with atrasentan completely prevented changes in cavernosal reactivity in DOCA-salt rats and restored the decreased ICP/MAP, completely preventing ED in DOCA-salt rats.

Conclusion

Activation of the ET-1/ET(A) pathway contributes to mineralocorticoid hypertension-associated ED. ET(A) receptor blockade may represent an alternative therapeutic approach for ED associated with salt-sensitive hypertension and in pathological conditions where increased levels of ET-1 are present."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.org/dc/terms/identifier"doi:10.1111/j.1743-6109.2008.01009.x"xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Rainey W.E."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Leite R."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Nunes K.P."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Tostes R.C."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Ergul A."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Clinton Webb R."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Carneiro F.S."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Carneiro Z.N."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Giachini F.R."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Lima V.V."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/author"Nogueira E.F."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/name"J Sex Med"xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/pages"2793-2807"xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/title"Activation of the ET-1/ETA pathway contributes to erectile dysfunction associated with mineralocorticoid hypertension."xsd:string
http://purl.uniprot.org/citations/18823320http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/18823320http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18823320
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