Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice

Petter Hedlund, Attila Aszódi, Alexander Pfeifer, Per Alm, Franz Hofmann, Marianne Ahmad, Reinhard Fässler, Karl Erik Andersson

Research output: Contribution to journalArticle

Abstract

The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP- dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot compensate for the absence of the cGMP/cGKI signaling cascade in vivo.

Original languageEnglish
Pages (from-to)2349-2354
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number5
DOIs
Publication statusPublished - Feb 29 2000

ASJC Scopus subject areas

  • Genetics
  • General

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    Hedlund, P., Aszódi, A., Pfeifer, A., Alm, P., Hofmann, F., Ahmad, M., Fässler, R., & Andersson, K. E. (2000). Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 97(5), 2349-2354. https://doi.org/10.1073/pnas.030419997