EFFECT OF THE SELECTIVE PHOSPHODIESTERASE TYPE 5 INHIBITOR SILDENAFIL ON ERECTILE FUNCTION IN THE ANESTHETIZED DOG

Purpose

The effects of sildenafil, a highly selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on erectile function in the anesthetized dog were evaluated.

Materials and Methods

In pentobarbital-anesthetized dogs, increases in intracavernosal pressure in the corpus cavernosum and penile blood flow were induced by pelvic nerve stimulation over a frequency range of 1 to 16 hertz. The effects of increasing doses of sildenafil on electrically stimulated intracavernosal pressure, penile blood flow, blood pressure, and heart-rate were evaluated. In parallel experiments, the effects of the nitric oxide synthase inhibitor N omega-Nitro-L-Arginine (L-NOArg) on these same parameters also were assessed.

Results

The effects of nerve stimulation on intracavernosal pressure and blood flow to the penis were blocked by L-NOArg, 0.1-3 mg./kg., in a dose-related manner, confirming the important role of nitric oxide in producing erections. Sildenafil, 1-100 micro g./kg administered intravenously, had no direct effect on intracavernosal pressure but potentiated the increase in intracavernosal pressure induced by nerve stimulation. This potentiation occurred at sildenafil plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of phosphodiesterase type 5 in vitro. Sildenafil had no significant effect on blood pressure or heart rate.

Conclusions

By inhibiting cyclic guanosine monophosphate-specific phosphodiesterase type 5, sildenafil augments the neuronal mechanism responsible for penile erection. This mechanism explains the significant improvements reported in the rigidity and duration of erections seen in patients with erectile dysfunction who have been treated with oral sildenafil.     

Thermographic assessment of patch-test responses

Infra-red thermography was used to quantify, at patch test sites, the allergic responses to experimental preparations of nickel sulphate and primary irritant responses to sodium lauryl sulphate in small groups of volunteers. The technique was also used to assess the patch-test responses in a much larger group of patients who had undergone routine patch testing for contact allergy with a wide range of test substances and among which there were large numbers of allergic, irritant and equivocal reactions. Thermographically, when compared to the surrounding normal skin surface, the sites of allergic reactions appeared as hot areas, the temperature and area of which were apparently dependent on the severity of the response. For allergic responses, there was a good correlation between the clinical assessment and either of two thermographic parameters, temperature and area of involvement. Compared with an aqueous solution of nickel sulphate, 'poor' formulations of the allergen, such as a suspension in soft paraffin base, elicited smaller and cooler reactions. Irritant reaction sites were not 'hot' and the temperature at such sites was no different from that of the surrounding normal skin. Infra-red thermography is a convenient non-invasive technique which apparently can be used to discriminate between irritant and allergic responses and to quantify the latter type of response.