PDE5 AND kidney

In the past years, PDE5 has emerged as a promising therapeutic target for many cancers due to its highly upregulated expression. Interestingly, a recent in vitro study by our group has shown the antitumor and chemopotentiating action of sildenafil against T cell lymphoma. Our study showed that lower doses of sildenafil (50 μM) and cisplatin (0.5 μg/mL) exhibited 4% and 23% cytotoxicity against HuT78 cells, respectively, which was dramatically increased up to 50% when treated with both...

The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea (OSA) induced damage remains unclear. Our study aimed to investigate the role of Pde5 in chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n=48) and Pde5 knockout (Pde5-/-) mice (n=24) were randomly assigned to CIH group and room air (RA) group. After 6 weeks, some WT mice (n=24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function...

BACKGROUND: Raynaud's phenomenon is a vasodilatory phenomenon characterised by digital pallor, cyanosis, and pain of the extremities. Primary Raynaud's phenomenon has no underlying disease associated with it, while secondary Raynaud's phenomenon is associated with connective tissue disorders such as systemic sclerosis. Systemic sclerosis causes fibrosis and commonly affects the skin and internal organs such as the gastrointestinal tract, lungs, kidney, and heart. Phosphodiesterase 5 inhibitors (PDE5i) are a class of drugs that increases blood flow to the extremities and may be beneficial in the treatment of Raynaud's phenomenon...

PURPOSE: Currently, there is a lack of research comparing tadalafil treatment protocols recommended during low-intensity shock wave therapy (LI-SWT) for patients with erectile dysfunction (ED) who are unresponsive to phosphodiesterase type 5 inhibitors (PDE5i). The objective of this study is to compare the efficacy of only LI-SWT versus LI-SWT plus 5 mg tadalafil daily versus LI-SWT plus 20 mg tadalafil alternate-day in PDE5i -resistant ED. MATERıALS AND METHODS: In this study, a cohort of 105 patients with PDE5i-resistant ED was recruited and divided into three groups labeled as A (only LI-SWT), B (LI-SWT plus 5 mg tadalafil daily), and C (LI-SWT plus 20 mg tadalafil alternate-day), comprising 27, 42, and 36 patients, respectively...

Background: Kidney-Yang deficiency syndrome (KDS) is a group of diseases related to hypothalamic-pituitary-adrenal (HPA) axis and sexual dysfunction. The folium of Epimedium brevicornu Maxim. (FEB) includes raw and prepared slices, named RFEB and PFEB, respectively. PFEB is traditionally believed to be good for tonifying kidney-Yang and improving sexual dysfunction. However, there are few studies comparing the pharmacological effects of RFEB and PFEB, and their underlying mechanisms. In this study, we aimed to compare the effects and safety of RFEB and PFEB on the HPA axis and sexual function...

AIMS: Phosphodiesterase 5 inhibitors (PDE5is) inhibit the hydrolysis of cyclic guanosine 5'-monophosphate in smooth muscle cells and are a widely known treatment for erectile dysfunction. Accumulating evidence also suggests that PDE5is exhibit potential benefits in cardiovascular and chronic kidney diseases. In this study, we examined the therapeutic effects of a PDE5i, vardenafil (VAR), in a focal segmental glomerulosclerosis (FSGS) mouse model. MATERIALS AND METHODS: FSGS was induced in BALB/c mice by the intravenous administration of Adriamycin (AD, 11 mg/kg of body weight)...

Reduced renal medullary oxygen supply is a key factor in the pathogenesis of acute kidney injury (AKI). As the medulla exclusively receives blood through descending vasa recta (DVR), dilating these microvessels after AKI may help in renoprotection by restoring renal medullary blood flow. We stimulated the NO-sGC-cGMP signalling pathway in DVR at three different levels before and after hypoxia/re-oxygenation (H/R). Rat DVR were isolated and perfused under isobaric conditions. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (10-6 mol/L) impaired cGMP degradation and dilated DVR pre-constricted with angiotensin II (Ang II, 10-6 mol/L)...

Hyperlipidemia plays an important role in the progression of kidney injury, likely due to renal lipotoxicity. The purpose of the present study was to investigate whether a phosphodiesterase 5a (PDE5a) inhibitor prevented lipid-induced injury through inhibiting endoplasmic reticulum (ER) stress and apoptosis in the kidney. In human proximal tubule HK2 cells, saturated fatty acid palmitic acid (PA) treatment for 24h markedly increased protein abundance of ER stress makers BiP and CHOP, which was associated with upregulated cleaved-caspase 3 expression and decreased ratio of Bcl2/Bax, two markers of apoptosis...

Podocyte injury is responsible for nephrotic syndrome. Previously, we found that tadalafil, a phosphodiesterase 5 inhibitor, might have protective effects on podocytes. Here, we investigated the effects of tadalafil in a nephrotic syndrome model and human podocyte cells. We divided adriamycin (ADR)-induced nephrotic syndrome model rats into the following groups: control + vehicle, control + tadalafil, ADR + vehicle, and ADR + tadalafil. The tadalafil-treated groups were orally administered 10 mg/kg tadalafil for 2 weeks...

Type 5 phosphodiesterase (PDE5) blockade by inhibitors (PDE5i) results in intracellular cyclic guanosine monophosphate (cGMP) increase and smooth muscle relaxation and are used for the treatment of men erectile dysfunction. Although they have high specificity for PDE5, these inhibitors are suspected to cross-interact also with cyclic adenosine monophosphate (cAMP)-specific PDEs, inducing the intracellular accumulation of this cyclic nucleotide and related testosterone increase, positively impacting male reproductive parameters...

BACKGROUND: Moringa oleifera Lam (MO) is native to India and is a cash crop widely cultivated in tropical and sub-tropical areas. The health improving properties of MO has been studied from a long time ago for the numerous phenolic compounds, including vitamins, flavonoids, phenolic acids, isothiocyanates, tannins and saponins, which are present in considerable amounts in the plant. A growing spectrum of therapeutic characteristics of MO leaves has been found and used in the remission or treatment of oxidative stress, liver disease, neurological disease, hyperglycemia and cancer...

Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18)...

The kidneys are vital organs that play an important role in removing waste materials from the blood, electrolyte balance, blood pressure regulation, and red blood cell genesis. Kidney disease can be caused by various factors, including diabetes, ischemia/reperfusion injury, and nephrotoxic agents. Inflammation and oxidative stress play a key role in the progression and pathogenesis of kidney diseases. Acute kidney injury (AKI) and chronic kidney disease (CKD) are important health problems worldwide, as they are associated with a long-term hospital stay, and increased morbidity and mortality in high-risk patients...

The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments. This is the case of sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor, which was originally designed to treat systemic hypertension and angina but is currently commercialized as erectile dysfunction treatment...

Phosphodiesterase 5 (PDE5) is one of the most extensively studied phosphodiesterases that is highly specific for cyclic-GMP hydrolysis. PDE5 became a target for drug development based on its efficacy for treatment of erectile dysfunction. In the present study, we synthesized four novel analogues of the phosphodiesterase type 5 (PDE5) inhibitor-tadalafil, which differs in (i) ligand flexibility (rigid structure of tadalafil vs. conformational flexibility of newly synthesized compounds), (ii) stereochemistry associated with applied amino acid building blocks, and (iii) substitution with bromine atom in the piperonyl moiety...

Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles...

INTRODUCTION: Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity)...

Sildenafil, approved two decades ago, is the inhibitor of phosphodiesterase 5 (PDE5). First of all, it was designated for angina pectoris, but soon it showed a wonderful efficacy in erectile dysfunction (ED) and then pulmonary arterial hypertension (PAH). Due to the distribution of phosphodiesterase (PDE) in almost all organs, maybe it effects other diseases. Hence, a great number of investigations began to understand the role of PDEi in different organs. Preliminary research on sildenafil in cell culture and animal models has yielded promising results...

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Hypertension increases kidney stress, which deteriorates function, and leads to peripheral renal vascular resistance. Long-term hypoperfusion promotes interstitial fibrosis and glomerular sclerosis, resulting in nephrosclerosis. Although hypertension and DN are frequent ESRD complications, relevant animal models remain unavailable. We generated a deoxycorticosterone acetate (DOCA)-salt hypertensive uni-nephrectomized (UNx) KKAy mouse model demonstrating hypertension, hyperglycemia, cardiac hypertrophy, kidney failure, increased urinary albumin creatinine ratio (UACR), and increased renal PDE4D and cardiac PDE5A mRNA levels...

Medicinal guide theory is a unique theory of Chinese medicine, which bears some similarities to the modern targeted drug delivery system. Modern pharmacological studies have revealed some scientific connotations of the essence of medicinal guide, which may be related to the changes of drug distribution and metabolism it induces. In modern medicine, phosphodiesterase type 5 (PDE5) inhibitors are widely used in the treatment of impotence or ED, with the main underlying mechanisms of increasing arterial blood supply and improving penile vascular endothelial function...