Intracavernous administration of SIN-1+VIP in an in vivo rabbit model for erectile function

Abstract

In accordance with the data reporting the identification of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) positive nerve fibres in the trabecular meshwork of the corpus cavernosum, we suggest that nitric oxide (NO) and VIP may serve complementary physiological roles in penile erection. Therefore SIN-1 and VIP were administered alone and in combination in an in vivo rabbit model. All rabbits revealed basal pressure values of 5 -8 cm H 2 O intracavernously. In the rabbits intracavernously (i.c.) injected with SIN-1 alone and VIP alone, no adequate erectile responses were observed. Whereas, in the group intracavernously injected with the combination of SIN-1 þ VIP, erectile responses with mean maximal intracavernous pressure (max. ICP) 52.8 ( AE 13.2) cm H 2 O were noted. These pressure elevations do not statistically diverge (P > 0.05) than the ones obtained in the control group administered i.c. injections of the combination of papaverine=phentolamine (mean max. ICP 51 ( AE 14.73) cm H 2 O). Referring to our results, we conclude that the combined use of SIN-1 þ VIP could play an important role in the physiological treatment of erectile dysfunction.

Erectile Dysfunction in Men on the Rise: Is There a Link with Endocrine Disrupting Chemicals?

“…6) [Ehmke et al, 1995;Andersson, 2001]. This is supported by injection of a combination of VIP and SIN-1 (NO-releasing compound) into the rabbit corpus cavernosum which augments the erectile response in vivo compared to those injected with SIN-1 or VIP alone, revealing an additive effect of the NO and VIP pathways [Sazova et al, 2002]. Overall, VIP is indisputably a smooth muscle relaxant and most likely complements NO-cGMP signalling via the cAMP pathway to promote tumescence (Fig.…”

Amelioration of diabetes‐induced cavernosal fibrosis by antioxidant and anti‐transforming growth factor‐β1 therapies in inducible nitric oxide synthase‐deficient mice

“…Perhaps the most surprising result was the inability of the long‐term administration of the long half‐life exogenous nitric oxide generator, molsidomine, to affect the SMC/collagen ratio, SMC content or apoptosis, that was expected from the antifibrotic effects reported for the kidney and liver [25–27]. Linked to the vasodilating activity, but still poor efficacy of the acute administration of molsidomine or its derivative SIN‐1 to induce corporal relaxation in comparison with prostaglandin E1 [46,47], this may rule out further consideration of this drug for erectile dysfunction. However, its antioxidant activity, both local and systemic, supports the view that iNOS is in fact antioxidant through a sustained production of nitric oxide in the corpora cavernosa.…”

Combination Pharmacotherapy in the Management of Patients with Hard-to-Treat Erectile Dysfunction

“…Alprostadil, combined with phentolamine and/or papaverine (Double Mix and Trimix), has in fact been part of the protocol in ICI therapy when response to alprostadil alone remains inadequate. Combination pharmacotherapy had been studied by using research animal models [3,4] and in various clinical settings [5–20], generally with favorable treatment outcome.…”