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PDE5 AND kidney

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https://www.readbyqxmd.com/read/27413196/the-role-of-cyclic-gmp-and-its-signaling-pathways-in-kidney-disease
#1
Kunyu Shen, David W Johnson, Glenda C Gobe
Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cyclic AMP and cyclic GMP (cGMP). There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease, via their downstream signaling, and these inhibitors also have known activity as anti-thrombotic and anti-cancer agents...
July 13, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27113485/phosphodiesterase-type-5-inhibition-reduces-albuminuria-in-subjects-with-overt-diabetic-nephropathy
#2
Wim Scheele, Susan Diamond, Jeremy Gale, Valerie Clerin, Nihad Tamimi, Vu Le, Rosalind Walley, Fernando Grover-Páez, Christelle Perros-Huguet, Timothy Rolph, Meguid El Nahas
Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy...
November 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27079836/role-of-phosphodiesterase-5-and-cyclic-gmp-in-hypertension
#3
REVIEW
Evanthia Mergia, Johannes Stegbauer
Cyclic GMP (cGMP) is a ubiquitous intracellular second messenger that mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular and nervous systems. Synthesis of cGMP occurs either by NO-sensitive guanylyl cyclases in response to nitric oxide or by membrane-bound guanylyl cyclases in response to natriuretic peptides and has been shown to regulate blood pressure homeostasis by influencing vascular tone, sympathetic nervous system, and sodium and water handling in the kidney...
April 2016: Current Hypertension Reports
https://www.readbyqxmd.com/read/26858657/inhibition-of-pde5-restores-depressed-baroreflex-sensitivity-in-renovascular-hypertensive-rats
#4
Clênia de Oliveira Cavalcanti, Rafael R Alves, Alessandro L de Oliveira, Josiane de Campos Cruz, Maria do Socorro de França-Silva, Valdir de Andrade Braga, Camille de Moura Balarini
Renal artery stenosis is frequently associated with resistant hypertension, which is defined as failure to normalize blood pressure (BP) even when combined drugs are used. Inhibition of PDE5 by sildenafil has been shown to increase endothelial function and decrease blood pressure in experimental models. However, no available study evaluated the baroreflex sensitivity nor autonomic balance in renovascular hypertensive rats treated with sildenafil. In a translational medicine perspective, our hypothesis is that sildenafil could improve autonomic imbalance and baroreflex sensitivity, contributing to lower blood pressure...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/26696017/novel-therapeutic-targets-for-phosphodiesterase-5-inhibitors-current-state-of-the-art-on-systemic-arterial-hypertension-and-atherosclerosis
#5
REVIEW
Elisardo C Vasquez, Agata L Gava, Jones B Graceli, Camille M Balarini, Bianca P Campagnaro, Thiago Melo C Pereira, Silvana S Meyrelles
The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature...
2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/26242375/phosphodiesterase-type-5-inhibitors-and-kidney-disease
#6
REVIEW
Baris Afsar, Alberto Ortiz, Adrian Covic, Abduzhappar Gaipov, Tarik Esen, David Goldsmith, Mehmet Kanbay
Chronic kidney disease (CKD) represents a worldwide health problem. Traditionally, the nephroprotective treatment for CKD aims to slow progression to end-stage renal disease and includes dietary protein restriction, correction of metabolic acidosis, and renin-angiotensin system blockers. However, current standard therapeutic options may not be enough for preventing CKD progression in a subset of patients making necessary to develop novel therapeutic options to further slow renal function loss. Phosphodiesterase type 5 (PDE5) inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension...
September 2015: International Urology and Nephrology
https://www.readbyqxmd.com/read/25426714/sildenafil-citrate-for-prophylaxis-of-nephropathy-in-an-animal-model-of-contrast-induced-acute-kidney-injury
#7
D Adam Lauver, E Grant Carey, Ingrid L Bergin, Benedict R Lucchesi, Hitinder S Gurm
Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI...
2014: PloS One
https://www.readbyqxmd.com/read/25420893/phosphodiesterase-type-5-inhibition-attenuates-cyclosporine-a-induced-nephrotoxicity-in-mice
#8
D Essiz, M Sozmen, M Sudagidan, A K Devrim
We investigated the renal protective effects of phophodiesterase type 5 (PDE5) inhibitors in mice with cyclosporine A (CyA; a calcineurin phosphatase inhibitor) induced nephrotoxicity. Fifty male mice were divided into five groups of 10. Group 1 received no treatment, group 2 received only saline orally, group 3 received 30 mg/kg/day CyA by subcutaneous injection, group 4 received only 30 mg/kg/day vardenafil orally, and group 5 received 30 mg/kg/day CyA by subcutaneous injection and 30 mg/kg/day vardenafil orally...
April 2015: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/24260450/phosphodiesterase-5-attenuates-the-vasodilatory-response-in-renovascular-hypertension
#9
Johannes Stegbauer, Sebastian Friedrich, Sebastian A Potthoff, Kathrin Broekmans, Miriam M Cortese-Krott, Ivo Quack, Lars Christian Rump, Doris Koesling, Evanthia Mergia
NO/cGMP signaling plays an important role in vascular relaxation and regulation of blood pressure. The key enzyme in the cascade, the NO-stimulated cGMP-forming guanylyl cyclase exists in two enzymatically indistinguishable isoforms (NO-GC1, NO-GC2) with NO-GC1 being the major NO-GC in the vasculature. Here, we studied the NO/cGMP pathway in renal resistance arteries of NO-GC1 KO mice and its role in renovascular hypertension induced by the 2-kidney-1-clip-operation (2K1C). In the NO-GC1 KOs, relaxation of renal vasculature as determined in isolated perfused kidneys was reduced in accordance with the marked reduction of cGMP-forming activity (80%)...
2013: PloS One
https://www.readbyqxmd.com/read/24042162/cgmp-selective-phosphodiesterase-inhibitors-stimulate-mitochondrial-biogenesis-and-promote-recovery-from-acute-kidney-injury
#10
Ryan M Whitaker, Lauren P Wills, L Jay Stallons, Rick G Schnellmann
Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours...
December 2013: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/23364806/phosphodiesterase-5-inhibition-attenuates-early-renal-ischemia-reperfusion-induced-acute-kidney-injury-assessment-by-quantitative-measurement-of-urinary-ngal-and-kim-1
#11
Rima Sohotnik, Omri Nativ, Abeer Abbasi, Hoda Awad, Victor Frajewicki, Bishara Bishara, Igor Sukhotnik, Zaher Armaly, Doron Aronson, Samuel N Heyman, Ofer Nativ, Zaid Abassi
Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11)...
April 15, 2013: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/23346948/phosphodiesterase-type-5-inhibitor-treatment-for-erectile-dysfunction-in-patients-with-end-stage-renal-disease-receiving-dialysis-or-after-renal-transplantation
#12
Fedele Lasaponara, Omid Sedigh, Giovanni Pasquale, Andrea Bosio, Luigi Rolle, Carlo Ceruti, Massimiliano Timpano, Carlo Luigi Augusto Negro, Matteo Paradiso, Annamaria Abbona, Giuseppe Paolo Segoloni, Dario Fontana
INTRODUCTION: The phosphodiesterase type 5 (PDE5) inhibitors are generally well tolerated and effective for treating erectile dysfunction (ED), including in patients with significant comorbidity. Because of this benign safety profile, investigators have used PDE5 inhibitors to treat patients with ED and severe renal disease or those who have received renal transplants. AIM: To assess safety and efficacy of PDE5 inhibitors in patients receiving dialysis or renal transplants...
November 2013: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/23171857/renoprotective-effects-of-sildenafil-in-doca-salt-hypertensive-rats
#13
Eun Hui Bae, In Jin Kim, Soo Yeon Joo, Eun Young Kim, Chang Seong Kim, Joon Seok Choi, Seong Kwon Ma, Suhn Hee Kim, Jong Un Lee, Soo Wan Kim
BACKGROUND/AIMS: Sildenafil, the first selective phosphodiesterase-5 (PDE5) inhibitor to be widely used for treating erectile dysfunction, has been investigated with regard to its cardioand renoprotective effects in animal models. This study further investigated the renoprotective effects of sildenafil and their molecular mechanisms in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats. METHODS: DOCA strips (200 mg/kg) were implanted in rats 1 week after unilateral nephrectomy...
2012: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/23143734/pde5-inhibition-against-acute-renal-ischemia-reperfusion-injury-in-rats-does-vardenafil-offer-protection
#14
Iason Kyriazis, George C Kagadis, Panagiotis Kallidonis, Ioannis Georgiopoulos, Antonia Marazioti, Aikaterini Geronasiou, Despοina Liourdi, George Loudos, Vasilios Schinas, Dimitris Apostolopoulos, Helen Papadaki, Christodoulos Flordellis, George C Nikiforidis, Andreas Papapetropoulos, Evangelos Nu Liatsikos
PURPOSE: To evaluate the effect of vardenafil on renal function after renal ischemia-reperfusion (IR) injury (IRI) in a rat model. MATERIALS AND METHODS: Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3-6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle...
June 2013: World Journal of Urology
https://www.readbyqxmd.com/read/22736111/the-effects-of-pde5-inhibitory-drugs-on-renal-ischemia-reperfusion-injury-in-rats
#15
A Küçük, M Yucel, N Erkasap, M Tosun, T Koken, M Ozkurt, S Erkasap
The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350 g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60 min, and then reperfused for 90 min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1 h before the induction of ischemia...
October 2012: Molecular Biology Reports
https://www.readbyqxmd.com/read/22059996/sildenafil-treatment-attenuates-lung-and-kidney-injury-due-to-overproduction-of-oxidant-activity-in-a-rat-model-of-sepsis-a-biochemical-and-histopathological-study
#16
E Cadirci, Z Halici, F Odabasoglu, A Albayrak, E Karakus, D Unal, F Atalay, I Ferah, B Unal
Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD-treated CLP group; (iii) CLP group; and (iv) sham-operated control group...
December 2011: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/22031848/sildenafil-reduces-polyuria-in-rats-with-lithium-induced-ndi
#17
Talita Rojas Sanches, Rildo Aparecido Volpini, Maria H Massola Shimizu, Ana Carolina de Bragança, Fabíola Oshiro-Monreal, Antonio Carlos Seguro, Lúcia Andrade
Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase...
January 1, 2012: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/21537421/systemic-and-metabolic-effects-of-pde5-inhibitor-drugs
#18
Antonio Aversa
Phosphodiesterase type-5 inhibitor (PDE5-i) drugs were first marketed in 1998 (sildenafil) for 'ondemand' treatment of male erectile dysfunction (ED) of any origin. They selectively inhibit intrapenile PDE5 isoenzyme which in turn increases intracellular cyclic guanosine monophosphate levels, thus resulting in prolonged relaxation of cavernosum smooth muscle cells and facilitating the erectile process. Since 2003, two new molecules (tadalafil and vardenafil) have been introduced, resulting in greater interest in these compounds and leading patients to ask for more prescriptions from their doctors...
March 15, 2010: World Journal of Diabetes
https://www.readbyqxmd.com/read/20981315/penile-involvement-in-systemic-sclerosis-new-diagnostic-and-therapeutic-aspects
#19
Antonio Aversa, Roberto Bruzziches, Davide Francomano, Edoardo Rosato, Felice Salsano, Giovanni Spera
Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ''sclerodermic penis"...
2010: International Journal of Rheumatology
https://www.readbyqxmd.com/read/20668100/increased-renal-phosphodiesterase-5-activity-mediates-the-blunted-natriuretic-response-to-a-nitric-oxide-donor-in-the-pregnant-rat
#20
Jennifer M Sasser, Xi-Ping Ni, Michael H Humphreys, Chris Baylis
Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0...
October 2010: American Journal of Physiology. Renal Physiology
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