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

Carneiro, Fernando Silva; Giachini, Fernanda Regina Casagrande; Lima, Victor Vitorino; Carneiro, Zidonia N.; Nunes, Kenia Pedrosa; Ergul, Adviye; Leite, Romulo; Tostes, Rita de Cassia Aleixo; Webb, Robert Clinton

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

Date

2008

Authors

Carneiro, Fernando Silva

Giachini, Fernanda Regina Casagrande

Lima, Victor Vitorino

Tostes, Rita de Cassia Aleixo

Webb, Robert Clinton

Abstract

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.

Keywords

Rho-kinase, Atrasentan

Citation

CARNEIRO, F. S. et al. DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosum. Canadian Journal of Physiology and Pharmacology, v. 86, p. 320-328, 2008. Disponível em: <https://www.nrcresearchpress.com/doi/10.1139/Y08-031#.Xclvj1VKjm4>. Acesso em: 10 jan. 2017.