1. ¹Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy
2. ²Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Departments of Pharmacology and Clinical Physiopathology, University of Florence, Florence, Italy
3. ³Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy
4. ⁴Endocrinology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy

Correspondence: Dr M Maggi, Andrology Unit, Physiopathology, viale Pieraccini, 6 Florence, Florence 50139, Italy. E-mail: m.maggi@dfc.unifi.it

Received 13 February 2007; Revised 26 June 2007; Accepted 26 June 2007; Published online 16 August 2007.

Abstract

Hypoxia is a normal, physiological condition in penile tissue, which is interrupted by reoxygenation associated to sleep-related erections. We previously described in the rat that a penile fibrosis and overexpression of the pro-fibrotic endothelin-1 type B receptor (ETB) are associated to prolonged (3 months) hypoxia induced by the bilateral surgical resection of the cavernous nerves (bilateral cavernous neurotomy (BCN)). The aim of the present study was to define the time frame in which BCN induces hypoxia and ETB overexpression in the penile tissue. In addition, we studied the time-dependency of the rescuing effect of an acute administration of the phosphodiesterase type 5 inhibitor, sildenafil. We found that BCN induced penile hypo-oxygenation (immunohistochemistry for Hypoxyprobe), penile ETB mRNA overexpression (quantitative real-time reverse transcriptase polymerase chain reaction) and hypersensitivity to the ETB agonist IRL-1620 (in vitro contractility study). Sildenafil treatment was able to counteract all these alterations (penile hypoxygenation, hyper-sensitivity to IRL-1620 and ETB overexpression), with its effect being more evident the earlier it was administered.