Analysis of Erectile Responses to BAY 41-8543 and Muscarinic Receptor Stimulation in the Rat
Article first published online: 18 SEP 2012
© 2012 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 10, Issue 3, pages 704–718, March 2013
How to Cite
Lasker, G. F., Pankey, E. A., Allain, A. V., Dhaliwal, J. S., Stasch, J.-P., Murthy, S. N. and Kadowitz, P. J. (2013), Analysis of Erectile Responses to BAY 41-8543 and Muscarinic Receptor Stimulation in the Rat. Journal of Sexual Medicine, 10: 704–718. doi: 10.1111/j.1743-6109.2012.02912.x
- Issue published online: 4 MAR 2013
- Article first published online: 18 SEP 2012
- sGC Stimulator;
- BAY 41-8543;
- Erectile Function;
- Muscarinic Receptors;
- Cavernosal Nerve Stimulation;
- Increased cGMP
Introduction. Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs.
Aim. The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions.
Methods. Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat.
Main Outcome Measures. Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated.
Results. The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response.
Conclusion. These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED. Lasker GF, Pankey EA, Allain AV, Dhaliwal JS, Stasch J-P, Murthy SN, and Kadowitz PJ. Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat. J Sex Med 2013;10:704–718.