Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF. 2003

Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
Fundación para la Investigación y el Desarrollo en Andrología. 28304, Madrid, Spain. isdtejada@terra.es

Standard treatments for erectile dysfunction (ED) (i.e., PDE5 inhibitors) are less effective in diabetic patients for unknown reasons. Endothelium-dependent relaxation (EDR) of human corpus cavernosum (HCC) depends on nitric oxide (NO), while in human penile resistance arteries (HPRA) endothelium-derived hyperpolarizing factor (EDHF) and NO participate. Here we show that diabetes significantly reduced EDR induced by acetylcholine (ACh) in HCC and HPRA. Relaxation attributed to EDHF was also impaired in HPRA from diabetic patients. The PDE5 inhibitor, sildenafil (10nM), reversed diabetes-induced endothelial dysfunction in HCC, but not in HPRA. Calcium dobesilate (DOBE; 10 microM) fully reversed diabetes-induced endothelial dysfunction in HPRA by specifically potentiating the EDHF-mediated component of EDR. Impairment by diabetes of NO and EDHF-dependent responses precluded the complete recovery of endothelial function in HPRA by sildenafil. This could explain the poor clinical response to PDE5 inhibitors of diabetic men with ED and suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men.

UI MeSH Term Description Entries
D007172 Erectile Dysfunction The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction. Impotence,Male Impotence,Male Sexual Impotence,Dysfunction, Erectile,Impotence, Male,Impotence, Male Sexual,Sexual Impotence, Male
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010413 Penis The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. Glans Penis,Penis, Glans
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011687 Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

Related Publications

Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
February 2004, Naunyn-Schmiedeberg's archives of pharmacology,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
May 2004, Naunyn-Schmiedeberg's archives of pharmacology,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
May 2012, Canadian journal of physiology and pharmacology,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
July 1990, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
January 2021, Reproduction (Cambridge, England),
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
January 2010, Advances in pharmacology (San Diego, Calif.),
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
June 1986, Circulation research,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
October 1989, Biochemical and biophysical research communications,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
June 2020, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Javier Angulo, and Pedro Cuevas, and Argentina Fernández, and Sonia Gabancho, and Antonio Allona, and Antonio Martín-Morales, and Ignacio Moncada, and Sebastián Videla, and Iñigo Sáenz de Tejada
October 2011, Phytotherapy research : PTR,
Copied contents to your clipboard!