NO-donating oximes relax corpora cavernosa through mechanisms other than those involved in arterial relaxation.

Autor: Pauwels B; Department of Pharmacology, Ghent University, Ghent, Belgium., Boydens C, Decaluwé K, Van de Voorde J
Jazyk: angličtina
Zdroj: The journal of sexual medicine [J Sex Med] 2014 Jul; Vol. 11 (7), pp. 1664-74. Date of Electronic Publication: 2014 May 19.
DOI: 10.1111/jsm.12564
Abstrakt: Introduction: Erectile dysfunction (ED), as well as many cardiovascular diseases, is associated with impaired nitric oxide (NO) bioavailability. Recently, oxime derivatives have emerged as vasodilators due to their NO-donating capacities. However, whether these oximes offer therapeutic perspectives as an alternative NO delivery strategy for the treatment of ED is unexplored.
Aims: This study aims to analyze the influence of formaldoxime (FAL), formamidoxime (FAM), and cinnamaldoxime (CAOx) on corporal tension and to elucidate the underlying molecular mechanisms.
Methods: Organ bath studies were carried out measuring isometric tension on isolated mice corpora cavernosa (CC), thoracic aorta, and femoral artery. After contraction with norepinephrine (NOR), cumulative concentration-response curves of FAL, FAM, and CAOx (100 nmol/L-1 mmol/L) were performed.
Main Outcome Measures: FAL-/FAM-induced relaxations were evaluated in the absence/presence of various inhibitors of different molecular pathways.
Results: FAL, FAM, and CAOx relax isolated CC as well as aorta and femoral artery from mice. ODQ (soluble guanylyl cyclase-inhibitor), diphenyliodonium chloride (nonselective flavoprotein inhibitor), and 7-ethoxyresorufin (inhibitor of CYP450 1A1 and NADPH-dependent reductases) substantially blocked the FAL-/FAM-induced relaxation in the arteries but not in CC. Only a small inhibition of the FAM response in CC was observed with ODQ.
Conclusions: This study shows for the first time that NO-donating oximes relax mice CC. Therefore, oximes are a new group of molecules with potential for the treatment of ED. However, the underlying mechanism(s) of the FAL-/FAM-induced corporal relaxation clearly differ(s) from the one(s) involved in arterial vasorelaxation.
(© 2014 International Society for Sexual Medicine.)
Databáze: MEDLINE
Externí odkaz: