title: Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix.
abstract: 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. In vivo erectile function was measured as intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP) following electrical stimulation of the cavernosal nerve. Venoocclusion was assessed by the maintenance of elevated in vivo ICP following intracorporal saline infusion. Vasoreactivity of isolated cavernosum in response to contractile and dilatory stimulation was examined in vitro by myography. Collagen and elastin content were evaluated by quantification of hydroxyproline and desmosine, respectively, as well as by quantitative PCR and histological analysis of isolated cavernosum. Erectile function was significantly decreased in db/db vs. BKS mice in a manner consistent with impairments in venoocclusive ability and decreased inflow. Heightened vasoconstriction and attenuated dilation in cavernosum of db/db vs. BKS mice suggest an overall lowered relaxation ability and thus impaired filling of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as lowered mRNA levels for tropoelastin, fibrillin-1, and alpha1(I) collagen were detected. These vasoreactive and sinusoidal matrix alterations may alter tissue compliance dispensability, preventing the normal expansion necessary for erection.
authors.affiliation: Department of Urology, University of Washington, 300 Ninth Avenue, Seattle, WA 98104, USA.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Luttrell
authors.forename: Mei
authors.initials: M
authors.lastname: Swee
authors.forename: Barry
authors.initials: B
authors.lastname: Starcher
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.forename: Kanchan
authors.initials: K
authors.lastname: Chitaley
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003895:Desmosine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009213:Myography; D009929:Organ Size; D010413:Penis / Q000098:blood supply* / Q000294:innervation / Q000473:pathology; D010656:Phenylephrine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D012039:Regional Blood Flow; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D054411:Receptors, Leptin; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C515447:leptin receptor, mouse; D003895:Desmosine; D010656:Phenylephrine; D003094:Collagen; D004549:Elastin; D000109:Acetylcholine; D006909:Hydroxyproline