1. ¹Department of Physiology and Physiopathology, Ghent University, Ghent, Belgium
2. ²Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent, Belgium
3. ³Department of Molecular Biology, Ghent University, Ghent, Belgium
4. ⁴Department of Anesthesia and Critical Care, Anesthesia Center for Critical Care Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: Professor J Van de Voorde, Department of Physiology and Physiopathology, Ghent University, De Pintelaan 185, Ghent 9000, Belgium. E-mail: johan.vandevoorde@UGent.be

Received 19 September 2007; Revised 18 October 2007; Accepted 1 November 2007; Published online 6 December 2007.

Abstract

Soluble guanylyl cyclase (sGC) is the major effector molecule for nitric oxide (NO) and as such an interesting therapeutic target for the treatment of erectile dysfunction. To assess the functional importance of the sGC₁₁ isoform in corpus cavernosum (CC) relaxation, CC from male sGC₁^{- /-} and wild-type mice were mounted in organ baths for isometric tension recording. The relaxation to endogenous NO (from acetylcholine, bradykinin and electrical field stimulation) was nearly abolished in the sGC₁^{- /-} CC. In the sGC₁^{- /-} mice, the relaxing influence of exogenous NO (from sodium nitroprusside and NO gas), BAY 41-2272 (NO-independent sGC stimulator) and T-1032 (phosphodiesterase type 5 inhibitor) were also significantly decreased. The remaining exogenous NO-induced relaxation seen in the sGC₁^{- /-} mice was significantly decreased by the sGC-inhibitor 1H-[ 1,2,4] oxadiazolo[ 4,3-a] quinoxalin-1-one. The specificity of the impairment of the sGC-related responses was demonstrated by the unaltered relaxations seen with forskolin (adenylyl cyclase activator) and 8-pCPT-cGMP (cGMP analog). In conclusion, the sGC₁₁ isoform is involved in corporal smooth muscle relaxation in response to NO and NO-independent sGC stimulators. The fact that there is still some effect of exogenous NO in the sGC₁^{- /-} mice suggests the contribution of (an) additional pathway(s).