Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA).

Background: The association between subclinical cardiovascular disease and subsequent development of erectile dysfunction (ED) remains poorly described.

Hypothesis: Among multiple subclinical atherosclerosis and vascular dysfunction measurements, coronary artery calcium (CAC) score best predicts ED.

Methods: After excluding participants taking ED medications at baseline, we studied 1862 men age 45 to 84 years free of known cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) with comprehensive baseline subclinical vascular disease phenotyping and ED status assessed at MESA visit 5 (9.

Glutathione (GSH) and the GSH synthesis gene Gclm modulate plasma redox and vascular responses to acute diesel exhaust inhalation in mice.

Context: Inhalation of fine particulate matter (PM₂.₅) is associated with acute pulmonary inflammation and impairments in cardiovascular function. In many regions, PM₂.

T- and L-type voltage-gated calcium channels: their role in diabetic bladder dysfunction.

Aims: We investigated the mechanisms of diabetic bladder dysfunction (BD) through analysis of the roles of L- and T-type voltage-gated calcium channels (VGCCs), with the ultimate goal of identifying potential drug targets for diabetic BD.

Methods: Bladder function of db/db (type 2 diabetes) and wild type (Wt) mice was evaluated by behavioral tests and in vivo cystometry. Contractile responses of bladder strips to carbachol were measured with or without pre-treatment with nifedipine (a L-type VGCC blocker) or mibefradil (a T-type VGCC blocker).

Genetics of erectile dysfunction.

Purpose: Erectile dysfunction affects 50% of men older than 40 years. Recently more attempts have been made to identify genetic predictors of this disease. We reviewed animal and human data on genes related to the development and increased risk of erectile dysfunction.

Common pitfalls in some of the experimental studies in erectile function and dysfunction: a consensus article.

Introduction: Experimental studies investigating physiology of erectile function and pathophysiology erectile dysfunction employ several in vitro and in vivo techniques. As the field of sexual medicine expanding, the proper conduct of such techniques is becoming an even more important necessity than before.

Aim: This review article aims to guide scientists, particularly young researchers and new comers in the field, toward employment of these techniques in an appropriate, timely, and competent fashion.

Glutathione (GSH) and the GSH synthesis gene Gclm modulate vascular reactivity in mice.

Oxidative stress has been implicated in the development of vascular disease and in the promotion of endothelial dysfunction via the reduction in bioavailable nitric oxide (NO()). Glutathione (GSH) is a tripeptide thiol antioxidant that is utilized by glutathione peroxidase (GPx) to scavenge reactive oxygen species such as hydrogen peroxide and phospholipid hydroperoxides. Relatively frequent single-nucleotide polymorphisms (SNPs) within the 5' promoters of the GSH synthesis genes GCLC and GCLM are associated with impaired vasomotor function, as measured by decreased acetylcholine-stimulated coronary artery dilation, and with increased risk of myocardial infarction.

Altered bladder function in elastin-deficient mice at baseline and in response to partial bladder outlet obstruction.

Objective: • To examine functional and molecular changes of the bladders from elastin-haploinsufficient mice (Eln(+/-) ) at baseline as well as in response to partial bladder outlet obstruction (pBOO).

Materials And Methods: • Female Eln(+/-) and wild type (Wt) mice (3-4 months old) were studied. • The bladder elastin content was quantified by measuring desmosine.

Characterization of erectile function in elastin haploinsufficicent mice.

Introduction: Elastin fibers confer passive recoil to many tissues including the lung, skin, and arteries. In the penis, elastin is present in sinusoids, arterioles, and in the tunica albuginea. Although decreased penile elastin has been reported in men with erectile dysfunction, the exact role of elastin in physiologic processes integral to erection remains speculative.

Helper-dependent adenovirus is superior to first-generation adenovirus for expressing transgenes in atherosclerosis-prone arteries.

Objective: Vascular gene transfer is a powerful tool for investigating and treating vascular diseases; however, its utility is limited by brevity of transgene expression and vector-associated inflammation. Helper-dependent adenovirus (HDAd), an advanced-generation adenovirus that lacks all viral genes, is superior to first-generation adenovirus (FGAd) in normal rabbit arteries. We compared HDAd to FGAd in arteries of cholesterol-fed rabbits, a model of early atherogenesis in which transgene expression might be decreased, and inflammation increased.

Anatomy, physiology, and pathophysiology of erectile dysfunction.

Introduction: Significant scientific advances during the past 3 decades have deepened our understanding of the physiology and pathophysiology of penile erection. A critical evaluation of the current state of knowledge is essential to provide perspective for future research and development of new therapies.

Aim: To develop an evidence-based, state-of-the-art consensus report on the anatomy, physiology, and pathophysiology of erectile dysfunction (ED).

Constriction of carotid arteries by urokinase-type plasminogen activator requires catalytic activity and is independent of NH(2)-terminal domains.

Urokinase-type plasminogen activator (uPA) is expressed at increased levels in stenotic, atherosclerotic human arteries. However, the biological roles of uPA in the artery wall are poorly understood. Previous studies associate uPA with both acute vasoconstriction and chronic vascular remodeling and attribute uPA-mediated vasoconstriction to the kringle - not the catalytic - domain of uPA.

Diabetes, obesity and erectile dysfunction: field overview and research priorities.

Purpose: We provide an overview of basic, clinical and epidemiological research in the field of erectile dysfunction and important research priorities presented at the 2009 National Institute of Diabetes and Digestive and Kidney Diseases symposium on Urological Complications of Diabetes and Obesity.

Materials And Methods: Experts in molecular biology, physiology, pharmacology, clinical trials, epidemiology and urological surgery highlighted current knowledge on erectile dysfunction associated with diabetes mellitus and obesity.

Results: Predictable associations between erectile dysfunction, and poor diabetic control and modifiable risk factors, including body mass index, have not yet been translated into randomized trials in the United States.

Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function.

To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC.

Mechanoregulation of proliferation.

The proliferation of all nontransformed adherent cells is dependent upon the development of mechanical tension within the cell; however, little is known about the mechanisms by which signals regulated by mechanical tension are integrated with those regulated by growth factors. We show here that Skp2, a component of a ubiquitin ligase complex that mediates the degradation of several proteins that inhibit proliferation, is upregulated when increased mechanical tension develops in intact smooth muscle and that its upregulation is critical for the smooth muscle proliferative response to increased mechanical tension. Notably, whereas growth factors regulate Skp2 at the level of protein stability, we found that mechanical tension regulates Skp2 at the transcriptional level.

Type 1 and Type 2 diabetic-erectile dysfunction: same diagnosis (ICD-9), different disease?

Introduction: Although hyperglycemia is a common defining feature of both type 1 and type 2 diabetes, many unique characteristics distinguish these diseases, including insulin and lipid levels, obesity status, and inflammatory agent profiles. In the laboratory, the presence of erectile dysfunction (ED) has been established in animal models of both type 1 and type 2 diabetes.

Aim: The purpose of this study was to determine whether unique mechanisms underlie ED in type 1 vs.

Review type 2 diabetes mellitus and erectile dysfunction.

Introduction: Diabetes mellitus (DM) is a major risk factor for the development of erectile dysfunction (ED). Although most diabetic ED cases are in patients with type 2 diabetes (T2DM), the majority of basic science studies examining mechanisms of diabetic ED have been conducted in animal models of type 1 diabetes.

Aim: Recently, however, clinical and laboratory-based studies have uncovered some key underlying factors of T2DM-associated ED, which we have compiled in this review of T2DM ED.

Strain differences in susceptibility to in vivo erectile dysfunction following 6 weeks of induced hyperglycemia in the mouse.

Introduction: With the large-scale availability of transgenic and knockout mouse models, the use of mice may greatly facilitate the examination of the mechanisms underlying diabetic erectile dysfunction (ED). Although in vitro studies of the mouse cavernosum show impairment of vasoreactivity, to date, no studies have demonstrated the in vivo impairment of erectile function in diabetic mice.

Aim: To establish whether mouse models of type I diabetes exhibit in vivo ED.

Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix.

The number of men with type II diabetes-associated erectile dysfunction (ED) continues to grow rapidly; however, the majority of basic science studies has examined mechanisms of ED in animal models of type I diabetes. In this study, we first establish an in vivo mouse model of type II diabetic ED using the leptin receptor mutated db/db and wild-type control BKS mouse. Furthermore, we hypothesized that dual mechanistic impairments contribute to the impaired erectile function in the type II diabetic mouse, altered vasoreactivity, and venoocclusive disorder.

Fluid shear stress-induced nitric oxide production in human cavernosal endothelial cells: inhibition by hyperglycaemia.

Objective: To investigate whether fluid shear stress (FSS) induces endothelial nitric oxide synthase (eNOS) activity and NO production in isolated human corpus cavernosal endothelial cells (HCCECs), and whether this response is altered during hyperglycaemia in vitro, as haemodynamic signalling during penile erection induces eNOS-mediated NO production in vivo.

Materials And Methods: ECs were cultured from HCC and characterized by the uptake of acetylated low-density lipoprotein and the expression of von Willebrand factor, VE-cadherin, CD31 and eNOS. HCCECs were exposed to FSS (1.

[Effect of topical application of a Rho-kinase inhibitor on the erectile response in rats].

Objective: To investigate the effect of Rho-kinase inhibitor applied topically on the penile erection and systemic circulation of rats.

Methods: Y-27632 was applied to the surface of the tunica albuginea or to the penile skin of rats, and the changes of CCP/MAP were observed continuously.

Results: Both methods of drug administration resulted in a marked increase in the erectile response both with and without stimulation of the innervation of the penile vasculature.

RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction.

Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis.

Vasodilator-stimulated phosphoprotein regulates proliferation and growth inhibition by nitric oxide in vascular smooth muscle cells.

Objective: Vasodilator-stimulated phosphoprotein (VASP) was identified as a substrate for cGMP-dependent protein kinase (PKG) and cAMP-dependent protein kinase (PKA). It is preferentially phosphorylated at serine239 by PKG, whereas serine157 is a preferred phosphorylation site for PKA. In addition, serine157 is phosphorylated by PKC in response to serum.

Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats.

We previously reported the inhibition of Rho-kinase to result in increased intracavernosal pressure (ICP) in an in vivo rat model of erection. Expression of an upstream activator of Rho-kinase, RhoA, has been demonstrated in the penile vasculature; however, the functional role of RhoA in the regulation of erection remains unknown. We used adeno-associated viral gene transfer of a dominant negative RhoA mutant (T19NRhoA) into rat cavernosum to test the hypothesis that RhoA activation is physiologically important for maintenance of the non-erect state and inhibition of this pathway leads to erection.

Microtubule depolymerization facilitates contraction of rat aorta via activation of Rho-kinase.

This study tests the hypothesis that microtubule (MT) depolymerization facilitates contraction of rat aorta via activation of Rho-kinase. Aortic rings from Sprague-Dawley rats were placed in a muscle bath for the measurement of isometric force generation. Bath temperature was decreased from 37 to 10-20 degrees C (30 min), inducing MT depolymerization.