DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin

• Published in: Canadian journal of physiology and pharmacology Vol. 86; no. 6; pp. 320 - 328
• Main Authors: Carneiro, Fernando S, Giachini, Fernanda R.C, Lima, Victor V, Carneiro, Zidonia N, Nunes, Kênia P, Ergul, Adviye, Leite, Romulo, Tostes, Rita C, Webb, R. Clinton
• Format: Journal Article
• Language: English
• Published: 01.06.2008
• Subjects: atrasentan; corps caverneux; corpus cavernosum; DOCA-salt hypertension; endothelin-1; endothéline-1; ERK1/2; hypertension DOCA-sel; receptor; Rho-kinase; récepteur ET
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/Y08-031

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 ET A 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 ET A 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 ET B 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/ET A receptor-independent mechanisms.