Nitric oxide release in penile corpora cavernosa in a rat model of erection. (1/478)

1. Nitric oxide (NO) levels were measured in the corpus cavernosum of urethane-anaesthetized rats by using differential normal pulse voltammetry with carbon fibre microelectrodes coated with a polymeric porphyrin and a cation exchanger (Nafion). A NO oxidation peak could be recorded at 650 mV vs. a Ag-AgCl reference electrode every 100 s. 2. This NO signal was greatly decreased by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), given by local and systemic routes, and enhanced by the NO precursor L-arginine. Treatment with L-arginine reversed the effect of L-NAME on the NO peak. 3. Both the NO signal and the intracavernosal pressure (ICP) were increased by electrical stimulation of cavernosal nerves (ESCN). However, the rise in the NO levels long outlived the rapid return to baseline of the ICP values at the end of nerve stimulation. 4. The ICP and the NO responses to ESCN were suppressed by local and systemic injections of L-NAME. Subsequent treatment with L-arginine of L-NAME-treated animals restored the NO signal to basal levels and the NO response to ESCN. The ICP response to ESCN was restored only in part by L-arginine. 5. The observed temporal dissociation between the NO and ICP responses could be accounted for by several factors, including the buffering of NO by the blood filling the cavernosal spaces during erection. 6. These findings indicate that an increased production of NO in the corpora cavernosa is necessary but not sufficient for maintaining penile erection and suggest a complex modulation of the NO-cGMP-cavernosal smooth muscle relaxation cascade.  (+info)

Nitric oxide and penile erection in streptozotocin-diabetic rats. (2/478)

The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ)-diabetic Sprague-Dawley rats, and the function of the NO-generating system in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague-Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by measuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was determined in corporal tissue by measuring the generation of [3H]citrulline from [3H]arginine. Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment, but this could be prevented by a short (2-week) pretreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a 2-week, but not by a 1-week, pretreatment with insulin; however, at 9 months after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots in pithed rats was enhanced in diabetic animals. This enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of insulin treatment. The inhibition of the stimulation-induced increase in corporal pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6-8 months of diabetes. In conclusion, STZ-induced diabetes caused changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irreversible. NO synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).  (+info)

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction. (3/478)

The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.  (+info)

Selective nitrergic neurodegeneration in diabetes mellitus - a nitric oxide-dependent phenomenon. (4/478)

1. In vitro and in vivo studies have demonstrated a dysfunctional nitrergic system in diabetes mellitus, thus explaining the origin of diabetic impotence. However, the mechanism of this nitrergic defect is not understood. 2. In the penises of streptozotocin (STZ)-induced diabetic rats, here, we show by immunohistochemistry that nitrergic nerves undergo selective degeneration since the noradrenergic nerves which have an anti-erectile function in the penis remained intact. 3. Nitrergic relaxation responses in vitro and erectile responses to cavernous nerve stimulation in vivo were attenuated in these animals, whereas noradrenergic responses were enhanced. 4. Activity and protein amount of neuronal nitric oxide synthase (nNOS) were also reduced in the penile tissue of diabetic rats. 5. We, thus, hypothesized that NO in the nitrergic nerves may be involved in the nitrergic nerve damage, since only the nerves which contain neuronal NO synthase underwent degeneration. 6. We administered an inhibitor of NO synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), in the drinking water of rats for up to 12 weeks following the establishment of diabetes with STZ. 7. Here we demonstrate that this compound protected the nitrergic nerves from morphological and functional impairment. Our results show that selective nitrergic degeneration in diabetes is NO-dependent and suggest that inhibition of NO synthase is neuroprotective in this condition.  (+info)

Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males. (5/478)

Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful therapy for male erectile dysfunction (ED) of different aetiology. Recently, sildenafil has been shown to restore erections in temporary ED related to the need of semen collection for assisted reproductive techniques. In this study, we investigated whether sildenafil administration modifies seminal parameters and/or erectile function in normal healthy volunteers. In a double-blind, randomized, placebo-controlled, cross-over two period investigation we enrolled 20 healthy male volunteers (mean +/- SE age 32 +/- 0.5 years). Subjects were not using any medication for the 3 month period prior to the study and were engaged in a stable relationship with proven fertility. The effects of sildenafil (100 mg) on seminal parameters and erectile function after audiovisual sexual stimulation were evaluated by semen analysis and by colour-Duplex ultrasound (the Resistive Index) respectively. In all subjects, sildenafil caused no changes in seminal and erection parameters when compared to placebo. Interestingly, sildenafil administration led to a marked reduction of the post-ejaculatory refractory time (10.8 +/- 0.9 min versus 2.6 +/- 0.7 min for placebo and sildenafil respectively; P < 0.0001). These results indicate that in normal subjects acute sildenafil treatment does not modify semen characteristics and has a positive influence over the resumption of erections following ejaculation in the presence of a continuous erotic stimulus.  (+info)

Diagnostic evaluation of erectile dysfunction. (6/478)

Erectile dysfunction, the persistent inability to attain or maintain penile erection sufficient for sexual intercourse, affects millions of men to various degrees. The majority of cases have an organic etiology, most commonly vascular disease that decreases blood flow into the penis. Regardless of the primary cause, erectile dysfunction can have a negative impact on self-esteem, quality of life and interpersonal relationships. The initial step in evaluation is a detailed medical and social history, including a review of medication use. Discussion with the patient's sexual partner may clarify exacerbating issues. The physical examination focuses on the cardiovascular, neurologic and urogenital systems. Laboratory tests are useful to screen for common etiologic factors and, when indicated, to identify hypogonadal syndromes. Appropriate evaluation of erectile dysfunction leads to accurate advice, management and referral of patients with erectile dysfunction.  (+info)

Effects of intracavernous administration of selective antagonists of alpha(1)-adrenoceptor subtypes on erection in anesthetized rats and dogs. (7/478)

The proerectile properties of three novel alpha(1)-adrenoceptor (alpha(1)-ADR) antagonists with different profiles of selectivity for the alpha(1)-ADR subtypes have been evaluated in anesthetized rats and dogs on intracavernous (IC) injection, in comparison with prazosin and phentolamine. In rats, the tested compounds decreased blood pressure (BP) and increased IC pressure (ICP), as well as the ratio ICP/BP. Rec 15/2841 (alpha(1a)- plus alpha(1L)-ADR-selective antagonist) and Rec 15/2615 (alpha(1b)-ADR selective) were the most potent compounds. The ICP/BP ratios calculated after injection of Rec 15/3039 (alpha(1d)-ADR selective) were not markedly different from those observed after vehicle injection. Prazosin and phentolamine proved poorly active, their main effect being hypotension. Approximate ED(25) values (dose of compound in micrograms inducing 25% increase of ICP/BP ratio) were Rec 15/2615 (22 microgram/kg)>= Rec 15/2841 (29 microgram/kg) > prazosin (136 microgram/kg) > phentolamine (1298 microgram/kg) > Rec 15/3039 (9600 microgram/kg). Submaximal stimulation of the cavernous nerve elicited an ICP rise whose amplitude was not altered by Rec compounds. In contrast, prazosin and phentolamine decreased this ICP rise. All compounds but 15/3039 induced significant increase of the ICP/BP ratio in dogs. Rec 15/2615 proved to be the most interesting compound, inducing significant increases of ICP/BP at doses practically devoid of effects on BP. The rank order of potency in dog in increasing the ICP/BP ratio was similar to that observed in rats. Only at the highest doses tested, all compounds, except Rec 15/3039, decreased the ICP rise elicited by submaximal stimulation of the cavernous nerve. Our data demonstrate that the alpha(1b)- and alpha(1L)-ADR subtypes are functionally relevant for the erectile function in these models, and that alpha(1b)- and/or alpha(1L)-ADR subtypes selective antagonists could represent a real advantage in erectile dysfunction therapy.  (+info)

Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. (8/478)

The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot compensate for the absence of the cGMP/cGKI signaling cascade in vivo.  (+info)