title: Altered contractility of rabbit penile corpus cavernosum smooth muscle by hypoxia.
abstract: OBJECTIVE
  To investigate the effects of severe hypoxia on trabecular smooth muscle contractility.
  
  
  METHODS
  Strips of rabbit corpus cavernosum were mounted in organ chambers to measure isometric tension. In some experiments intracellular free Ca2+ concentration and tension were measured by the intracellular fluorescent dye FURA-2 and isometric tension recording simultaneously.
  
  
  RESULTS
  Contractions elicited by norepinephrine, endothelin-1 or potassium were attenuated under hypoxic conditions (pO2 approximately 10 mm. Hg). Strips contracted with 20 mM. K+ under normoxic conditions and then exposed to hypoxia consistently lost the potassium-induced tone. The hypoxia-induced relaxation was not affected by the removal of the endothelium, by treatment with the cyclooxygenase blocker, indomethacin, or with the guanylate cyclase blocker, methylene blue. The potassium channel opener, cromakalim, and adenosine relaxed potassium contracted strips; however, the potassium channel blockers glibenclamide, apamin, barium chloride and charybdotoxin or the adenosine receptor antagonist 8-(p-sulfonyl)theophylline were unable to prevent hypoxia-induced relaxation. Tetraethylammonium, a potassium channel blocker, and the depolarizing agents ouabain and high potassium (80 mM.), partially prevented hypoxia-induced relaxation. The calcium ionophore, ionomycin, had no effect on hypoxia-induced relaxations. Hypoxia, within 2 to 6 minutes, caused a large accumulation in intracellular calcium, concomitant with a loss of trabecular smooth muscle tone. Both these effects could be reproduced by inhibiting oxidative phosphorylation with 2,4,dinitrophenol. Reoxygenation resulted in an immediate recovery of both tone and intracellular calcium levels. Tissues under hypoxic conditions for 30 minutes had a 24% and 67% decrease in the ATP/ADP ratio and in creatine phosphate concentrations, respectively.
  
  
  CONCLUSIONS
  Hypoxia causes a simultaneous increase in intracellular calcium and relaxation which, we propose, is the consequence of inhibition of oxidative phosphorylation with loss of high energy phosphates, necessary for the homeostasis of Ca2+ and the contractile mechanism of the cavernosal smooth muscle.
authors.affiliation: Department of Urology, Boston University School of Medicine, Massachusetts, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Kim
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Hypolite
authors.forename: J F
authors.initials: JF
authors.lastname: García-Díaz
authors.forename: G A
authors.initials: GA
authors.lastname: Broderick
authors.forename: K
authors.initials: K
authors.lastname: Tornheim
authors.forename: J T
authors.initials: JT
authors.lastname: Daley
authors.forename: R
authors.initials: R
authors.lastname: Levin
authors.forename: I
authors.initials: I
authors.lastname: Saenz de Tejada
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000503:physiopathology*; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D016232:Endothelins; D007476:Ionophores; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D010725:Phosphocreatine; D010042:Ouabain; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine