Emotional stress can precipitate severe, reversible left ventricular dysfunction in patients without coronary disease. Exaggerated sympathetic stimulation is probably central to the cause of this syndrome.

Introduction Priapism describes a persistent erection arising from dysfunction of mechanisms regulating penile tumescence, rigidity, and flaccidity. A correct diagnosis of priapism is a matter of urgency requiring identification of underlying hemodynamics. Aims To define the types of priapism, address its pathogenesis and epidemiology, and develop an evidence-based guideline for effective management. Methods Six experts from four countries developed a consensus document on priapism; this document was presented for peer review and debate in a public forum and revisions were made based on recommendations of chairpersons to the International Consultation on Sexual Medicine. This report focuses on guidelines written over the past decade and reviews the priapism literature from 2003 to 2009. Although the literature is predominantly case series, recent reports have more detailed methodology including duration of priapism, etiology of priapism, and erectile function outcomes. Main Outcome Measures Consensus recommendations were based on evidence-based literature, best medical practices, and bench research. Results Basic science supporting current concepts in the pathophysiology of priapism, and clinical research supporting the most effective treatment strategies are summarized in this review. Conclusions Prompt diagnosis and appropriate management of priapism are necessary to spare patients ineffective interventions and maximize erectile function outcomes. Future research is needed to understand corporal smooth muscle pathology associated with genetic and acquired conditions resulting in ischemic priapism. Better understanding of molecular mechanisms involved in the pathogenesis of stuttering ischemic priapism will offer new avenues for medical intervention. Documenting erectile function outcomes based on duration of ischemic priapism, time to interventions, and types of interventions is needed to establish evidence-based guidance. In contrast, pathogenesis of nonischemic priapism is understood, and largely attributable to trauma. Better documentation of onset of high-flow priapism in relation to time of injury, and response to conservative management vs. angiogroaphic or surgical interventions is needed to establish evidence-based guidance.

The molecular mechanism for priapism is not well characterized. Although the nitric oxide (NO) pathway is known to mediate penile erection under normal conditions, we hypothesized that the mechanism of priapism rests in aberrant downstream signaling of this pathway based on our previous findings that mice lacking the gene for endothelial nitric oxide synthase (eNOS ؊/؊ ) and mice lacking both neuronal NOS (nNOS) and eNOS (nNOS ؊/؊ , eNOS ؊/؊ ) have a tendency for priapic activity. We investigated the role of downstream guanylate cyclase and phosphodiesterase type 5 (PDE5A) expression and function in mediating these responses in eNOS ؊/؊ and nNOS ؊/؊ , eNOS ؊/؊ mice. Erectile responses to both cavernous nerve stimulation and intracavernosal injection of the NO donor diethylamine-NONOate were augmented in eNOS ؊/؊ and nNOS ؊/؊ , eNOS ؊/؊ mice but not in WT or nNOS ؊/؊ mice. PDE5A protein expression and activity and cGMP levels were significantly lower in eNOS ؊/؊ and nNOS ؊/؊ , eNOS ؊/؊ mice, and this effect was reproduced in WT corpus cavernosum exposed to NOS inhibitors. Moreover, cavernous nerve stimulation was associated with a marked augmentation of cavernosal cGMP levels, suggesting that, although lower at baseline, the production of cGMP is unchecked in eNOS ؊/؊ and nNOS ؊/؊ , eNOS ؊/؊ mice upon neurostimulation. Transfection of eNOS ؊/؊ mice with an adenovirus encoding eNOS resulted in a normalization of PDE5A protein and activity as well as a correction of priapic activity. Coupled with the observation that sickle cell disease mice (which show a priapism phenotype) evince dysregulated PDE5A expression͞activity, these data suggest that PDE5A dysregulation is a fundamental mechanism for priapism.endothelial nitric oxide synthase ͉ gene transfer ͉ sickle cell disease

Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA͞Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA͞Rho-kinase contributes to diabetesrelated erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rhokinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA͞Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZdiabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA͞Rho-kinase in the penis, we evaluated the effects of an adenoassociated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA͞Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA͞Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA͞Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA͞Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.gene therapy ͉ neuronal NO synthase ͉ endothelium R elaxation of corporal smooth muscle is essential for normal erectile function, and evidence exists to implicate neuronaland endothelial-derived nitric oxide (NO) as the principal mediator of corporal smooth muscle relaxation (1-3). Impairments in neurogenic and endothelium-dependent corporal smooth muscle relaxation is observed in diabetes mellitus and is responsible for erectile impairment in diabetic patients (4, 5).Contraction of smooth muscle is primarily mediated by phosphorylation of the regulatory myosin light chain (MLC) by the Ca 2ϩ ͞calmodulin-dependent activation of MLC kinase and actin͞myosin cross-bridge formation (6). Relaxation is mediated by the dephosphorylation of MLC by smooth muscle myosin phosphatase. Recent evidence has established the importance of Ca 2ϩ -sensitization through the Ca 2ϩ -independent stimulation of MLC kinase or the attenuation of MLC phosphatase activity (7). A principle regulator of MLC phosphatase is the serine͞ threonine kinase, Rho-kinase. Data from peripheral arteries suggest that RhoA, a GTP-binding protein, mediates agonistinduced activation of Rho-kinase (8). The exchange of GDP for GTP on RhoA and translocation of RhoA from the cytosol to the membrane are markers of activation, and enable the downstr...