DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosurn


Autoria(s): CARNEIRO, Fernando S.; GIACHINI, Fernanda R. C.; LIMA, Victor V.; CARNEIRO, Zidonia N.; NUNES, Kenia P.; ERGUL, Adviye; LEITE, Romulo; TOSTES, Rita C.; WEBB, R. Clinton
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2008

Resumo

The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade of ETA receptors prevents abnormal responses of the corpus cavernosum in DOCA-salt hypertension. Male C57BL/6 mice were unilaterally nephrectomized and treated for 5 weeks with both DOCA and water containing 1% NaCl and 0.2% KCl. Control mice were uninephrectomized and received tap water with no added salt. Animals received either the ETA antagonist atrasentan (5 mg.day(-1).kg(-1) body weight) or vehicle. DOCA-salt mice displayed increased systolic blood pressure (SBP), and treatment with atrasentan decreased SBP in DOCA-salt mice. Contractile responses in cavernosal strips from DOCA-salt mice were enhanced by ET-1, phenylephrine, and electrical field stimulation (EFS) of adrenergic nerves, whereas relaxations were not altered by IRL-1620 (an ETB agonist), acetylcholine, sodium nitroprusside, and EFS of nonadrenergic noncholinergic nerves. PD59089 (an ERK1/2 inhibitor), but not Y-27632 (a Rho-kinase inhibitor), abolished enhanced contractions to ET-1 in cavernosum from DOCA-salt mice. Treatment of DOCA-salt mice with atrasentan did not normalize cavernosal responses. In summary, DOCA-salt treatment in mice enhances cavernosal reactivity to contractile, but not to relaxant, stimuli, via ET-1/ETA receptor-independent mechanisms.

Identificador

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, v.86, n.6, p.320-328, 2008

0008-4212

http://producao.usp.br/handle/BDPI/24241

10.1139/Y08-031

http://dx.doi.org/10.1139/Y08-031

Idioma(s)

eng

Publicador

NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Relação

Canadian Journal of Physiology and Pharmacology

Direitos

restrictedAccess

Copyright NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Palavras-Chave #endothelin-1 #ETA receptor #Rho-kinase #DOCA-salt hypertension #corpus cavernosum #ERK1/2 #atrasentan #DEOXYCORTICOSTERONE ACETATE-SALT #ANGIOTENSIN-CONVERTING ENZYME #ERECTILE DYSFUNCTION #PENILE ERECTION #BLOOD-PRESSURE #UP-REGULATION #HYPERTENSION #RECEPTORS #RAT #CONTRACTION #Pharmacology & Pharmacy #Physiology
Tipo

article

proceedings paper

publishedVersion