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

Fernando S. Carneiro, Fernanda R.C. Giachini, Victor V. Lima, Zidonia N. Carneiro, Kênia P. Nunes, Adviye Ergul, Romulo Leite, Rita C. Tostes, R. Clinton Webb

Research output: Contribution to journalArticle

21 Scopus citations

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 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 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.

Original languageEnglish (US)
Pages (from-to)320-328
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Volume86
Issue number6
DOIs
StatePublished - Jun 1 2008

    Fingerprint

Keywords

  • Atrasentan
  • Corpus cavernosum
  • DOCA-salt hypertension
  • ERK1/2
  • ET receptor
  • Endothelin-1
  • Rho-kinase

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Carneiro, F. S., Giachini, F. R. C., Lima, V. V., Carneiro, Z. N., Nunes, K. P., Ergul, A., Leite, R., Tostes, R. C., & Webb, R. C. (2008). DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosum. Canadian Journal of Physiology and Pharmacology, 86(6), 320-328. https://doi.org/10.1139/Y08-031