Aging is an important risk factor for impotence in men. Because nitric oxide (NO) appears to be the mediator of corpora cavernosal smooth muscle relaxation, we have examined in 5-, 20-, and 30-mo-old rats, designated "adult," "old," and "senescent," respectively, whether aging causes a decrease of erectile response that may correlate with lower NO synthase (NOS) in the penis. Electric field stimulation (EFS) of the cavernosal nerve showed that the maximum intracavernosal pressure (MIP) declined in the old and senescent rats to 80 and 51% of the adult value, respectively. A low systemic dose of the NOS inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME; 2 mg/kg), reduced the MIP by only 38% in the adult rats but decreased it in the old and senescent rats by 72 and 80%, respectively. In the absence of EFS, intracavernosal papaverine (phosphodiesterase inhibitor), or nitroglycerin (NO donor), caused a lower erectile response in the old and senescent rats compared with the adult animals (MIP: 41 and 14%, respectively; duration of the erection 46 and 21%, respectively). Tissue sections from old and senescent penises showed increasing degrees of sclerotic degeneration. In comparison with the adult rats, the penile soluble NOS activity per gram of tissue that is sensitive to L-NAME decreased significantly by 63% in the senescent rats but was elevated in the old rats. These results indicate that aging causes an erectile failure due to factors initially independent from an impairment of penile NO synthesis but which are compounded in the very old rats by the decrease of penile NOS activity.
In 2 patients receiving bone marrow transplantation sodium 2-mercaptoethane sulfonate has proved efficacious in preventing the serious problem of cyclophosphamide cystitis by regional detoxification of acrolein. We detail the first use of sodium 2-mercaptoethane sulfonate in the United States. We are cautiously enthusiastic and optimistic that the simultaneous administration of sodium 2-mercaptoethane sulfonate and cyclophosphamide will decrease if not eliminate cyclophosphamide-induced carcinoma.
The ability of 2-mercaptoethane sodium sulfonate to prevent histologic damage to the bladder from cyclophosphamide was studied. Male rats receiving 2-mercaptoethane sodium sulfonate in conjunction with cyclophosphamide had a statistically significant decrease in ulceration, inflammation and edema of the bladder compared to those treated with cyclophosphamide alone. Most bladders of animals given prophylactic 2-mercaptoethane sodium sulfonate with a dose of cyclophosphamide were histologically indistinguishable from controls receiving neither drug. The relevance of these findings to the short and long-term effects of cyclophosphamide on the urothelium is discussed.
The mainstay of therapy for interstitial cystitis (IC) is intravesical instillation of dimethylsulfoxide (DMSO). Although numerous clinical studies have documented symptomatic improvement in up to 70% of patients, the mechanism of action, and effect on objective parameters of bladder function have not been adequately studied. In this study we have used the in vitro whole bladder model to determine the effect of DMSO on several parameters of bladder function, including in vitro cystometry, pressure generation, and ability to empty in response to both field stimulation and bethanechol. All parameters measured were significantly (P < 0.05) reduced. Bladder capacity was reduced by a mean of 18.71%. Compliance was markedly decreased after instillation of DMSO. The magnitude of pressure generated in response to field stimulation was decreased from a mean of 8.93 cm H20 to a mean of 5.55 cm H20. In response to bethanechol, the magnitude of pressure generation was decreased from a mean of 9.85 cm H 2 0 to a mean of 7.07 cm H 2 0 after treatment with DMSO. The rate of pressure generation in response to field stimulation was substantially reduced by 46.6%. In response to field stimulation and bethanechol, control bladders emptied 86% and 92%, respectively. After treatment with DMSO, these values were reduced by an average of 33.24% and 14.92%, respectively. This in vitro study has shown that DMSO has a negative effect on multiple parameters of bladder function, including compliance, capacity, and contractile and functional responses to field stimulation and bethanechol.
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