title: Molecular and functional characterization of Kv 7 channels in penile arteries and corpus cavernosum of healthy and metabolic syndrome rats.
abstract: OBJECTIVE
  KCNQ-encoded voltage-dependent potassium channels (Kv 7) are involved in the regulation of vascular tone. In this study we evaluated the influence of Kv 7 channel activation on smooth muscle relaxation in rat penile arteries and corpus cavernosum from normal and spontaneously hypertensive, heart failure-prone (SHHF) rats - a rat model of human metabolic syndrome.
  
  
  METHODS
  Quantitative PCR and immunohistochemistry were used to determine the expression of KCNQ isoforms in penile tissue. Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from normal and SHHF rats.
  
  
  RESULTS
  Transcripts for KCNQ3, KCNQ4 and KCNQ5 were detected in penile arteries and corpus cavernosum. KCNQ1 was only found in corpus cavernosum. Immunofluorescence signals to Kv 7.4 and Kv 7.5 were found in penile arteries, penile veins and corpus cavernosum. The Kv 7.2-7.5 activators, ML213 and BMS204352, relaxed pre-contracted penile arteries and corpus cavernosum independently of nitric oxide synthase or endothelium-derived hyperpolarization. Relaxations to sildenafil, a PDE5 inhibitor, and sodium nitroprusside (SNP), an nitric oxide donor, were reduced by blocking Kv 7 channels with linopirdine in penile arteries and corpus cavernosum. In SHHF rat penile arteries and corpus cavernosum, relaxations to ML213 and BMS204352 were attenuated, and the blocking effect of linopirdine on sildenafil-induced and SNP-induced relaxations reduced. KCNQ3, KCNQ4 and KCNQ5 were down-regulated, and KCNQ1 was up-regulated in corpus cavernosum from SHHF rats. KCNQ1-5 transcripts remained unchanged in penile arteries from SHHF rats.
  
  
  CONCLUSIONS
  These data suggest that Kv 7 channels play a role in erectile function and contribute to the pathophysiology of erectile dysfunction, an early indicator of cardiovascular disease.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T A
authors.initials: TA
authors.lastname: Jepps
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S P
authors.initials: SP
authors.lastname: Olesen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|The Vascular Biology Research Centre, Institute of Cardiovascular and Cell Sciences, St George's, London, UK.
authors.forename: I A
authors.initials: IA
authors.lastname: Greenwood
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Dalsgaard
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000378:metabolism*; D051656:KCNQ Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D010413:Penis / Q000033:anatomy & histology / Q000098:blood supply* / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
chemical_list: D051656:KCNQ Potassium Channels