Intracavernosal administration of sodium nitrite as an erectile pharmacotherapy

It has been reported that sodium nitrite (NaN[O.sub.2]) can act as a storage form of nitric oxide (NO) that can have beneficial pharmacologic actions. The present study was undertaken to investigate the effects of NaN[O.sub.2] on erectile function in the rat. The intracavernosal (i.c.) injection of NaN[O.sub.2] produced dose-related increases in i.c. pressure and decreases in systemic arterial pressure. NaN[O.sub.2] was 1000-fold less potent than sodium nitroprusside in increasing i.c. pressure. Increases in i.c. pressure in response to NaN[O.sub.2] were attenuated by the nitric oxide synthase (NOS) inhibitor N-nitro-larginine methyl ester (L-NAME). The increases in i.c. pressure in response to NaN[O.sub.2] were not altered by the xanthine oxidoreductase inhibitor allopurinol. The decreases in systemic arterial pressure in response to i.c. injections of NaN[O.sub.2] were attenuated by allopurinol and were either unchanged or increased by L-NAME. These data suggest that NaN[O.sub.2] is converted to vasoactive NO in the corpora cavernosum and systemic vascular bed of the rat by different mechanisms. The present data suggest that the conversion of NaN[O.sub.2] to vasoactive NO is mediated by NOS in the corpora cavernosum and by xanthine oxidoreductase in the systemic vascular bed of the rat. These data show NaN[O.sub.2] can serve as a NO donor that increases erectile activity in the rat. Key words: sodium nitrite, nitric oxide, intracavernosal, erectile dysfunction, eNOS, xanthine oxidoreductase, vasodilator. Des etudes ont indique; que le nitrite de sodium (NaN[O.sub.2]) pourrait agir comme une forme de reserve de monoxyde d'azote (NO) ayant des actions pharmacologiques beneefiques. La presente etude a eu pour but d'examiner les effets du NaN[O.sub.2] sur la fonction erectile du rat. L'injection intracarverneuse (i.c.) de NaN[O.sub.2] a provoque des augmentations de pression i.c. et des diminutions de pression arteerielle systemique proportionnelles a la dose administree. Le NaN[O.sub.2] aete d'un facteur 1000 moins puissant que le nitroprussiate de sodium pour ce qui est d'augmenter la pression i.c. Les augmentations de pression i.c. en reponse au NaN[O.sub.2] ont ete attenueees par l'inhibiteur de la monoxyde d'azote synthase (NOS), N-nitro-L-arginine methyl ester (L-NAME), et n'ont pas ete modifiees par l'inhibiteur de la xanthine oxydoreductase, allopurinol. Les diminutions de pression arterielle systemique en reponse aux injections i.c. de NaN[O.sub.2] ont ete attendes par l'allopurinol,et n'ont pas ete modifiees ou ont ete augmenteees par L-NAME. Ces resultats donnent a penser que le NaN[O.sub.2] est converti en NO vasoactif dans le corps caverneux et dans le lit vasculaire systemique du rat par des meecanisme differents. Ils laissent supposer que la conversion du NaN[O.sub.2] en NO vasoactif est vehiculee par NOS dans le corps caverneux et par la xanthine oxydoreductase dans le lit vasculaire systemique du rat. Enfin, ils montrent que le NaN[O.sub.2] peut agir comme un donneur de NO qui augmente l'activite erectile chez le rat. Mots-cles: nitrite de sodium, monoxyde d'azote, intracaverneux, dysfonction erectile, eNOS, xanthine oxydoreductase, vasodilatateur. [Traduit par la Redaction]
Introduction Erectile dysfunction (ED) is a common multifactorial disorder in which the male cannot achieve or maintain a penile erection adequate for sexual relations. Although ED is classified as a [...]